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Smoldyn 2.0 release updates features

February 25, 2009. MSI Research Fellow Steve Andrews this week released the latest version of Smoldyn, a stochastic spatial simulator. Version 2.0 include algorithms for accurate adsorption, desorption, and partial transmission. It also permits molecules with excluded volume. Input formats have been simplified for ease of use. Smoldyn 2.0 is freely accessible and can be downloaded at www.smoldyn.org.

Mechanism improves information transmission inside cells

Just as a phone or cable company tunes the performance of its lines to optimize transmission of Internet data, so do cells tune their own internal signaling lines.

So says an article in today's issue of Nature from researchers at the Molecular Sciences Institute (Yu et.al. 2008).  The team was headed by a trio of researchers: Richard Yu, Gustavo Pesce, and Roger Brent.

The mechanism of the tuning event is one known since the dawn of the computer age, negative feedback.  The concept was popularized (as "cybernetics") by the computer science pioneer Norbert Wiener.

The MSI researchers studied signal transmission in so called cell signaling system in the single-celled organism, Brewer's yeast.  Cell signaling systems sense and transmit information from outside the cell.  They are critical to many life processes, including those that cause cells to divide, to stop dividing, to commit suicide via programmed cell death, and to change into other cell types during development from a fertilized egg.  This new work shows that cells constantly adjust system operation to optimize the amount of information their signals carry, and suggests that similar information tuning mechanisms operate in other cells including human cells.

The work is significant because it provides a unifying explanation for one aspect of how different cell signaling systems operate. According to Professor Pamela Silver of the Harvard Department of Systems Biology, "The last 30 years of work by the biologists resulted in a great deal of detail about cell signaling systems.  Too much detail.  This work from MSI is significant precisely because it provides a simplifying explanation that ties together a great deal of this detail."

According to Silver, the work is also significant for another reason "All too often, biologists tried-- naively-- to apply concepts from computer science to understanding the function of biological systems.  This is a case where the application of concepts from computers actually explains something important.  There will be others."

Like many scientific investigations, the work raises more questions than it answers.  According to Brent, "This finding makes it imperative to fill in some remaining gaps: how the cells encode the information in the signal and how they generate and transmit the negative feedback they use to increase the bandwidth of the signaling channel.”

However, the work will likely lead to near term application in discovery of new drugs and in explanation of human disease.  Says Hiroaki Kitano of Sony Research Labs, "Ever since the 1980s, the discovery of new biological control mechanisms led to development of drugs targeted at those mechanisms within about ten years.  [The MSI work] is the first example of what may be a whole set of new control mechanisms.  I imagine that these will be important for disease and therapy by 2015 or 2020.  It's gratifying that those of us who came of age with computers will finally be able to contribute to this work."

The MSI research was funded by the US government, particularly the National Human Genome Research Institute as part of the Alpha Project, an interdisciplinary effort to understand the quantitative behavior of a model cell signaling system, the yeast pheromone response system.

The Molecular Sciences Institute is an independent nonprofit genomic research laboratory in Berkeley, California.  Work at MSI weaves physics, engineering, computer science, and mathematics together with biology and chemistry toward a goal of enabling precise, quantitative, prediction of the future behaviors of biological systems.  MSI is a Center of Excellence in Genomic Sciences funded by the United States National Human Genome Research Institute.

Dose-response optimization for signaling systems using HillSim.

November 22, 2008. MSI Research Fellow Steven Andrews announced the release of a new software package called HillSim. HillSim is a computer program for analyzing and optimizing signaling system models. It can be used to model arbitrarily complex networks including those with feedbacks, feedforwards and other complex relationships between signaling proteins.

While HillSim can simulate signaling system dynamics, it is best for analyzing their steady-state properties.  HillSim calculates steady-state dose-response behaviors for system nodes, fits them to Hill functions, and compares these Hill function fits to “target” dose-response behaviors that are provided by the user.  HillSim can also optimize the signaling system parameters so that the model dose-responses match the target dose-responses as closely as possible.

HillSim is developed and maintained by Steve Andrews.  It runs on Mac OS X, Linux, and Windows, and is available to the public under the GNU Lesser General Public License.

CQGF announces latest publication- The Alpha Project: a model system for systems biology research.

The article published in IET Systems Biology by Yu., et.al., is a comprehensive overview of the Alpha project, from its historical and theoretical underpinnings to its current state of conceptual and factual knowledge. The authors outline some of the most significant discoveries from the project and describe important portable experimental tools and conceptual frameworks that emerged from this work that can be readily applied towards similar types of analysis in other cellular signaling systems.

Cell-ID software update includes new graphical user interface and incorporates R statistical analysis package.

The most recent update to Cell-ID incorporates several new features and enhancements. Cell-ID 1.4 (release date October, 2008) incorporates a graphical user interface (Vcell-0.1), which provides easy testing options that help the user choose parameters to process experiments in batch mode, as well as bug fixes and improvements. This release also includes a new package, Rcell, to aid in the analysis of Cell-ID output files. Rcell contains a set of functions to load these files into R, filter out unwanted cells, display images and plot simple and compound variables.

A detailed protocol describing how to use Cell-ID to quantify cellular parameters from individual cells and track them over time will be available soon (Chernomoretz, A., Bush, A.,Yu, R.,Gordon, A., and Colman-Lerner, A., [2008] Using Cell-ID1.4 with R for microscope-based cytometry. Current Protocols in Molecular Biology).

MSI is newest member of the Association of Independent Research Institutes

June 9, 2008.  MSI is proud to annouce its acceptance as the newest member of the Association of Independent Research Institutes (AIRI). AIRI is an association of independent, not-for-profit biomedical and behavioral research institutes conducting federally funded research. Its mission is to enhance the ability of its members to improve human health and advance knowledge. 

Working notes for open West coast rapid response lab

December 28, 2007. MSI is now hosting working notes for discussions of an open west coast laboratory that develops technologies to allow rapid response to new infectious diseases. A number of wet and computational methods developed at MSI and the Center for Quantitative Genome Function are applicable to this problem and might contribute to addressing it.

MSI researchers a disclose a new method to increase the sensitivity of antibody-based assays

November 14, 2007. Researchers at the Molecular Sciences Institute present a novel and broadly applicable method to precisely quantify most mammalian antibodies. In a brief communication published in Nature Methods, Burbulis et.al., describe the construction of a ‘near universal’ protein-DNA chimera that couples the specificity of antibodies with a highly sensitive PCR based assay. The chimeric molecule, termed a tadpole (Burbulis, 2005), combines a double stranded DNA ‘tail’ with a protein ‘head’ assembled from domains of Peptostreptococcus sp. protein L and Streptococcus sp. protein G. This LG tadpole is ‘near universal’ because it is capable of recognizing most classes of mammalian immunoglobulinGs (IgG). It allows for accurate quantification of small numbers of antibodies by reducing signal noise. Burbulis and co-workers observed that the LG tadpole did not bind to avian IgYs and exploited this property to improve the detection limit and linear range of their assays. They used the LG tadpole to quantify numerous molecules and demonstrated the potential for clinical applications by quantifying levels of Prostate Specific Antigen (PSA) in clinical samples.  They used a commercially available anti-PSA IgG to detect PSA levels in human serum with 100 times the sensitivity of a comparable ELISA. It should now be possible to use the LG tadpole to convert any antibody-based assay to a PCR based assay that has enhanced sensitivity and dynamic range. [ Burbulis, et.al., 2007 ]

Genome Technology Young Investigator Spotlight features MSI Scientists. 

October 31, 2007. Each Wednesday Genome Technology highlights promising young investigators on its website. On October 31, 2007 Genome Technology featured IFIBYNE Investigator and Center for Quantitative Genome Function Co-investigator Alejandro Colman-Lerner. On October 3, 2007 they featured MSI Senior Research Fellow Ian Burbulis.

Roger Brent to speak at the 8th International Conference on Systems Biology

August 17, 2007. Dr. Roger Brent will give an invited talk at the 8th International Conference on Systems Biology to be held October 1-6 in Long Beach, California.

MSI President and Research Director Roger Brent to speak at the first q-bio Conference on Cellular Information Processing.

March 28, 2007. Dr. Roger Brent will give an invited  talk at the First q-bio Conference on Cellular Information Processing to be held  August 8-11, 2007 in Santa Fe, NM. Dr. Brent also gave a presentation entitled "Physiology and Genetic Regulation of Cellular Signal Transmission" at the Keystone Symposia on Systems Biology and Regulatory Networks (March 22-27, Steamboat Springs, CO).

First Bay Area Workshop on Data Driven Computational Analysis of Biological Networks to be  held April 13, 2007 at UCSF Mission Bay.

February 20, 2007. Registration is now open for the first Bay Area Workshop on Data-Driven Computational Analysis of Biological Networks. This workshop is intended to bring together Bay Area researchers who are interested in the problem of using computational techniques for biological network analysis. The first workshop will discuss and evaluate current methods for the extraction of causal relationships from biological data. Specifically, it will be a forum to identify challenges that face the field, both in terms of the nature of needed data and the necessary mathematical infrastructure. Special attention will be devoted to important applications of these methods, such as the establishment of causal relationships between human genetic variation and disease, in addition to the elucidation of general organizational principles in signal transduction and biological regulatory systems. The program will include 6 invited talks from leading experimental and theoretical researchers, a panel discussion and a reception. There will be much opportunity for extended discussion.The workshop is jointly sponsored by MSI and the QB3 Institute.

UPDATE 3/25/07: A poster session has been added to the workshop. Registered participants should send their poster title and abstract by email to :helsamadATbiochem.ucsf.edu

Registration is free but space is limited. To ensure your place, register on line as soon as possible.

Help us  spread the word- download a flyer [PDF] and post it today.

Applications for the 2007 Genomic Biology High School  Student Internship program now being accepted.

Update: The application process is now closed. We will be conducting interviews in early April.

January 2, 2007. We are now accepting applications for the MSI/Center for Quantitative Genome Function High School student internship program. This eight week summer internship program combines research and education in genomics and computational biology. The program is open to US citizens/permanent residents who are currently enrolled high school juniors or seniors. The program is scheduled to run from June 18-August 10, 2007. Applications are due March 9, 2007. See the internship webpage for more informaton about the internship, complete instructions on how to apply and links to the online applicaton form.

Miller Institute Fellow Annie Tsong joins MSI

December 7, 2006. Annie Tsong, Ph.D. joined MSI and the Alpha project as a visiting fellow in September 2006. Annie arrived from UC Berkeley where she is a Miller Institute Fellow working with Dr. Michael Eisen. Annie completed her graduate studies at the University of California San Francisco in the laboratory of Alex Johnson.  Her graduate work, in two landmark papers (Tsong, et.al., 2003;Tsong, et.al. 2006) pioneered the use of genetics and comparative genomics techniques to identify changes in cis and trans regulatory elements in yeast mating responsive genes that lead to the transition from positive regulation of mating in the human pathogen Candida albicansto negative regulation of mating in Saccharomyces cerevisiae (bakers yeast).  On the Alpha project, Tsong will study the differences that evolutionary divergence between pheromone system proteins and regulatory phosphorylation have made to key quantitative aspects of system behavior such as transmission time and feedback regulation.

Updated Cell ID 1.1, an open source software for cell finding, tracking and analysis, released

Updated 1/29/2007. Read about Cell ID 1.1 in Nature  Methods.

Andrew Gordon, MSI research fellow and leader of the Alpha project modeling group, today released an updated version of Cell-ID.  Cell ID is a sophisticated user-modifiable Open Source program to identify, track and capture data from single cells over time.  It can identify regularly shaped cells, such as yeast or human lymphocytes that form a dark boundary in brightfield microscope images and copies the cell parameters to the corresponding fluorescent image. It reports collected data in machine-readable text format that can be used as input data for open source data analysis programs such as PAW, R or ROOT, and is optimized to work with PAW. Its combined methods produce a powerful, open source microscope-based cytometry.  Scientists at MSI and elsewhere use Cell ID to obtain and analyze high throughput data from time course studies of single cells visualized in light microscopes.  Cell ID is an open source project, written in C and is released under the GNU Lesser General Public License.  Gordon is now interfacing the Cell-ID PAW package to work with the open source "microscope driver" software, Micromanager,( http://www.micro-manager.org/) by Nico Sturman, Nenand Amodaj, and Ron Veil at UCSF.

Former MSI high school interns garner honors

December 7,2006.  Two former MSI / CQGF high school interns received undergraduate awards this fall. Tyra Mcray (Summer 2003), a senior at UC Davis, received a Best Poster Presentation for her poster entitled "A genetic screen for kinases involved in dietary restriction and anti-aging behavior" that she presented at the Annual Biomedical Research Conference for Minority Students held November 8-11, 2006 in Anaheim, CA. Vi Vu (Summer 2006), a freshman at Harvard, was selected to participate in a research training program at Harvard. The Harvard program aims to prepare disadvantaged students for careers in science. It was devised by Dr. Richard Losick and is sponsored by the Howard Hughes Medical Institute. Vi will be partnered with a scientist-mentor and start work in a research lab in Harvard Molecular and Cellular Biology this spring the spring semester.

Alpha wiki page is launched

November 9,2006. The Alpha pheromone pathway modeling wiki page is now available on line. The Alpha wiki is a dynamic forum where a detailed description of the alpha pheromone signal transduction pathway is presented along with ongoing development and discussion of models, experiments and theories. Registered users can log on and contribute to modeling the yeast alpha pheromone signal transduction pathway.

New MSI website is launched

November 9,2006. MSI has released our new web site. The updated site significantly improves performance. The web site was developed by Digizyme.com. The custom images in the banners were created by Dawn Warfield.

MSI President speaks about security at PopTech!

Roger Brent speaks at the Annual PopTech! Conference in Camden, MA. (October, 2006).

MSI at the International Conference on Systems Biology

October 9, 2006. MSI scientists present seminars and workshops at the 7th International Conference on Systems Biology in Yokohama, Japan (October, 2006). MSI/CQGF scientists presented recent findings from the Alpha project and related work on the ECell project at the ICSB conference in October. CQGF Principal investigator, Roger Brent presented a talk entitled "Quantitative physiology of a cellular information sensing and relaying system". CQGF Co-investigator Alejandro Colman-Lerner presented a talk entitled "Sources and control of cell to cell variation in the response of yeast to mating pheromone". Koichi Takahashi presented a workshop covering the latest developments in the ECell project. Takahashi and Nathan Addy presented at a workshop. Nathan Addy described progress on integration of ECell with SBML at the SBML workshop. Takahashi and Addy also presented a tutorial on ECell.

MSI Announces its "Genomic Sciences Summer 2006 Internship" for High School Juniors and Seniors.

              The Molecular Sciences Institute is committed to training, motivating and mentoring future genomic scientists. Our Genomic Sciences Internship Program provides high school juniors and seniors an exceptional opportunity to gain hands-on experience in a genomics laboratory for eight weeks each summer. These competitive internships are sponsored by the National Human Genome Research Institute.   MSI combines genomic experimentation with computer modeling. The mission of MSI is to predict the behavior of cells and organisms in response to defined genetic and environmental changes. Progress toward this goal will significantly increase our understanding of biological systems and help catalyze radical changes in how diseases are understood and treated.   These 8-week internships are open to students who are high school juniors or seniors during the 2005-2006 academic year. Internships begin on Monday, June 19th and end on Friday, August 11th. After receiving a comprehensive introduction to genomics at MSI, students will complete a laboratory research project and give a final oral presentation. Eighty percent of a student's time will be spent at MSI doing research, learning about the backgrounds of our collaborators during "Meet the Scientists" presentations, participating in genomics workshops and a journal club, and attending MSI team meetings. Twenty percent of a student's time will be spent on MSI-sponsored scientific enrichment activities and fieldtrips throughout the Bay Area to supplement the student's learning. To learn about MSI interns from the summers of 2003, 2004 and 2005, please visit their web pages.  After completing the summer internship, students may also take advantage of ongoing individualized tutoring in science and mathematics provided by MSI throughout the following school year. In addition, MSI will pay for an SAT preparation course for the student.   Interns must be U.S. citizens or permanent residents.

              Applications are due by March 10, 2006. Interested students should send completed applications via postal mail or email to the addresses below. Two Recommendation Forms must also be sent on behalf of the student. These Recommendation Forms can be sent directly to MSI by the author or sent with the student's application packet/email.  Please call 510-981-8738 with questions.   Molecular Sciences Institute High School Student Internship, 2168 Shattuck Avenue - 2nd Floor, Berkeley, CA, 94704

  MSI announces discovery of mechanisms that keep cellular responses accurate  

              Dr. Roger Brent, President and Director of Research at The Molecular Sciences Institute (MSI), announced today that researchers at MSI have found that the behavior of individual cells are subject to unexpected sources of variability and discovered two mechanisms that can keep cellular responses accurate. The findings are detailed in Nature, released online September 18, 2005.

              The article, entitled "Regulated Cell to Cell Variation in a Cell Fate Decision System” describes new experimental and analytical methods that were instrumental in the discovery of two mechanisms that control the quantitative behavior of yeast.   "This innovative interdisciplinary work helps us understand and control the sources of performance variations in genetically identical yeast cells," said Dr. Brent. "Here, the best scientific understanding is yet to come, because the work lays this system open to the whole gamut of genetic approaches developed during the 20th century.  As it is, our work has significant implications for the understanding and engineering of biological systems and suggests new paths to development of therapies to combat disease."  "We were stunned when we realized that most of the variability in gene expression was due to an intrinsic cellular property that affects all genes," explained Dr. Alejandro Colman-Lerner, a biologist, who co-authored the paper with Dr. Andrew Gordon, a physicist. "I recall Andrew's initial astonishment at the unexpected dynamics of this system's variability; for him, with his experimental physics background, there was no doubt that there was something totally unexpected in our measurements."   "As we thought about it," continued Dr. Colman-Lerner, "the implications dawned on us. How could a cell manage to accurately control genes in response to a stimulus in the presence of this distortive variability? We will be busy answering this question for years, but we have already found signaling components that modulate variation and a rectifying feature of the system that corrects for some of the distortion. We are now pursuing a genetic approach to further characterize the molecular machinery controlling variability; and it's quite likely that our findings will be valid throughout biology."  Drs. Gordon and Colman-Lerner developed methods to accurately measure multiple color fluorescence in single cells imaged live over time in a sensitive microscopic setup. They studied the response of yeasts to mating pheromone, a signaling mechanism that allows yeast to sense each other's presence and activate a mating differentiation program. This cell-fate decision is a prototype for similar signaling mechanisms in animal development and human disease.   The goal of this research was to establish a quantitative experimental system to understand cellular signaling. It was undertaken in the context of MSI's Alpha Project, an effort of a multi-disciplinary team of researchers to understand the quantitative behavior of a cell signaling system using combined experimental and computational approaches.  The work presented in this paper aims at determining the basis for the cell-to-cell variation in the response of yeast to pheromone. Previous studies had shown that stochasticity in molecular events causes genes to have random variations in their output, which was attributed to a large effect of chance in processes that involve a small number of molecules. The implication was that chance in molecular processes would prove to be a major determinant of the widely observed variability of populations of genetically identical cells. Gordon and Colman-Lerner's powerful approach was to simultaneously measure the expression of genes activated by different regulatory molecules.  Their surprising finding was that regardless of what their regulation was, all genes showed an overlapping variation in their expression in individual cells, as if they were synchronized by an external source. This source of variation was likely acting on one or more of the common steps of gene expression shared by all of the genes measured, including RNA synthesis and translation. Chance, hence, played only a small role in the overall cell-to-cell variability of gene expression.  Could chance be an important factor in the events leading from pheromone binding to gene activation? Using the dual gene activity method, the MSI researchers peered, for the first time, into the variability conveyed by the individual gene's regulatory molecules. Again, the results pointed to a small role for chance, and showed the pathway's variability was largely determined by two key protein kinases that transmit the signal.  The Molecular Sciences Institute, Inc. is an independent nonprofit genomic research laboratory in Berkeley, California, that combines genomic experimentation with computer modeling. Work at MSI aims to weave physics, engineering, computer science, and mathematics together with biology and chemistry to enable precise, quantitative, prediction of the future behaviors of biological systems.  MSI is a Center of Excellence in Genomic Sciences funded by the United States National Human Genome Research Institute.

MSI and Amnis Announce Collaboration             

MSI Uses Amnis "ImageStream" Cell Analysis System Capabilities to Elucidate SignalingPathways in a Key Model Organism         

              The Molecular Sciences Institute (MSI) and Amnis Corporation today announced a collaboration to use Amnis' ImageStream 100 system to further elucidate signaling pathways in the model organism, S. cerevisiae, (yeast).  The project examines extra-to-intra-cellular information flow and processing to understand how cells receive, amplify, and integrate signals from a variety of stimuli, and is of potentially great impact to the scientific research community.    This effort, being conducted under the direction of Dr. Roger Brent, is part of MSI's ongoing Alpha Project, which is developing predictive models of biological systems to enable better understanding of the behavior of both cells and organisms.  Critical to the project are the unique capabilities of the ImageStream system, which combines the image quality of a microscope and the statistical power of a flow cytometer.    "Our work is aided by the novel capabilities of the Amnis ImageStream system, and will in turn aide Amnis to further develop its system to help researchers understand the complex processes underlying biological behaviors," said Dr. Roger Brent, president and director of the Molecular Sciences Institute.  "We look forward to sharing the results of this project with the larger scientific community, as well as exploring the many other ways that the ImageStream system may be able to facilitate predictive biology research." 

               MSI's immediate use for the instrument is centered on cell-to-cell variability experiments.  MSI also expects the instrument to facilitate the analysis and localization of post-translational modifications of pathway proteins and pathway complexes using affinity reagents and/or in vivo sensors.  In short order, the ImageStream will be of immense general use to the yeast community and the greater scientific community who are studying a variety of cells that can be analyzed in flow.  

              "We developed the ImageStream to enable a wide range of biomedical research that was previously not feasible," said David Basiji, CEO of Amnis Corporation.  "We are proud that as distinguished and innovative a research organization as MSI is using the ImageStream's unique capabilities."  ImageStream technology brings powerful new quantitative capability to the analysis of cells. In a typical run, the system collects data from tens of thousands of cells in just a few minutes, generating up to six simultaneous high-resolution images per cell, including brightfield, darkfield and as many as four independent fluorescent images. Over 200 data features are automatically calculated for every cell. Analysis of this rich data set is accomplished with Amnis' "IDEAS" statistical image analysis software, a package that was developed by the company to provide analytical power and flexibility along with exceptional ease-of-use.    ImageStream was commercially launched in December, 2004.  Contacts:  Amnis Corporation, David Basiji, Ph.D., President, (206) 374-7165  MSI, Roger Brent, Ph.D., President, (510)647-0690

MSI Visiting Research Fellow wins Human Frontier Fellowship       

Dr. Roger Brent, President and Director of Research at the Molecular Sciences Institute ("MSI"), announced that MSI Visiting Research Fellow, Kouichi Takahashi, Ph.D., has been awarded a Human Frontier Cross-Disciplinary Fellowship from The Human Frontier Science Foundation (HFSF).   The HFSF supports novel, innovative and interdisciplinary basic research focused on the complex mechanisms of living organisms; topics range from molecular and cellular approaches to systems and cognitive neuroscience. A clear emphasis is placed on novel collaborations that bring biologists together with scientists from fields such as physics, mathematics, chemistry, computer science and engineering to focus on problems at the frontier of the life sciences.  Dr. Takahashi was one of twelve recipients of the prestigious award this year.  Since the award's inception in 1989, eleven recipients have gone on to win the Nobel Prize.    "This Cross Disciplinary Fellowship will enable me to carry out a combined computational/in vivo measurement approach to the alpha signaling pathway”, Dr. Takahashi stated. The award provides support for up to three years of research.  He expects to begin the project at MSI in October 2005.      

Dr. Takahashi received his B.S., M.S., and Ph.D. in Bioinformatics from Keio University.  His thesis was entitled, "Multi-algorithm and multi-timescale cell biology simulation."  He is also a core founder of "E-cell Project," a scientific project developing theoretical supports, technologies, and software platforms necessary for molecular level whole-cell simulation.  Currently, he is a System Architect of  E-Cell Systems  at The Institute for Advanced Biosciences at Keio University in Japan.    The Molecular Sciences Institute is an independent nonprofit research laboratory that combines genomic experimentation with computer modeling.  Work at MSI aims to weave physics, engineering, computer science, and mathematics together with biology and chemistry to enable precise, quantitative, prediction of the future behaviors of biological systems.

MSI Releases "Moleculizer" - a new approach to simulation of intracellular biochemical networks                        

              Dr. Roger Brent, President and Director of Research at the Molecular Sciences Institute ("MSI"), announced today the release of a new approach to simulation of intracellular biochemical networks in the January, 2005  edition of Nature Biotechnology.  The research article, entitled "Automatic generation of cellular reaction networks with Moleculizer 1.0," describes MSI's discrete stochastic event simulator, which keeps track of the thousands of complex species formed from pathway proteins as it simulates reactions between them by a standard Monte Carlo method.  A distinguishing aspect of Moleculizer is its ability to generate protein complexes and reactions as they are needed, as opposed to generating all potential complexes and reactions all at once, a task that requires tremendous computational resources.  "Moleculizer is a powerful tool that meets a very real need for biologists," explained Dr. Brent.  "It is a critical step forward in our quest to provide an accurate simulation of intracellular biochemical networks."  "I've designed Moleculizer to be intuitive for biologists," said Dr. Larry Lok, a mathematician who conceived and programmed Moleculizer.  "Its parallel simplifications in simulation setup and output provide data in a way that is meaningful and useful to biological researchers."  Moleculizer was developed in the context of MSI's Alpha Project, an ambitious experimental and computational effort to understand the quantitative behavior of a cell signaling pathway in yeast.  The Alpha Project is funded by the National Institutes of Health's National Human Genome Research Institute, which designated MSI as a Center of Excellence in Genomic Research. The CEGS program supports multi-investigator, interdisciplinary research teams to develop novel and innovative genomic research projects.  "Moleculizer is exactly the sort of development that one wants to see from multidisciplinary work," explained Dr. Brent.  "The mathematical and algorithmic skills that Dr. Lok brought to the problem could only come from one with his strengths, but the work is important because it addresses a problem arising directly from the biology."  Dr. Daniel Gillespie, a pioneer in stochastic methods for modeling chemical kinetics stated, "Dr. Lok has succeeded in adapting and creatively extending earlier developed techniques for stochastically simulating chemical reactions so that they can be used to study real cellular systems, where the huge numbers of potential species and reaction channels makes things very difficult."  Computer simulations can be powerful tools in contemporary molecular biology research, aiding scientists in analyzing data and in testing hypotheses with simulated outcomes before testing them experimentally.  The predictive capabilities of computer simulations can also aid biologists in viewing cellular activity over a period of time, by taking advantage of the power of computers to generate the thousands of potential protein complexes and reactions that cells are able to generate.  The Molecular Sciences Institute is an independent nonprofit research laboratory that combines genomic experimentation with computer modeling.  Work at MSI aims to weave physics, engineering, computer science, and mathematics together with biology and chemistry to enable precise, quantitative, prediction of the future behaviors of biological systems.   In keeping with the MSI's support for an open source biology Moleculizer will be made freely available under the GNU Lesser General Public License.

Nature Biotechnology is "a monthly journal covering the science and business of biotechnology. It publishes new concepts in technology/methodology of relevance to the biological, biomedical, agricultural and environmental sciences as well as covers the commercial, political, ethical, legal, and societal aspects of this research.

MSI Reveals Invention for Detection and Precise Quantification of Molecules

              Researchers at The Molecular Sciences Institute revealed means for sensitive detection and precise quantification of arbitrarily designated molecules.  The work is published Nature Methods.  The cover article, entitled Using protein-DNA chimeras to detect and count small numbers of molecules”, describes "tadpole" molecules, and their use to detect and count small numbers of proteins and other molecules.    Detection and quantification methods based on these molecules have exquisite sensitivity, immense dynamic range, and unprecedented quantitative precision.  These attributes should make the molecules useful for applications from diagnosis and assessment of human disease, to environmental monitoring, to detection of pathogens during an emerging infectious disease or a deliberate biological attack.   Methods based on these molecules are designed to work with the existing infrastructure of PCR machines, which are widely deployed and found most county public health departments in the United States.    According to Dr. Roger Brent, MSI Director and senior member of the team, "We called the molecules tadpoles because they consist of a protein head coupled to a DNA tail.  The head binds the specific target molecule, while the DNA tail lets us count the number of target molecules."

              Dr. Ian Burbulis, a researcher at MSI, devised the tadpole molecules and is the first author of the paper.  According to Dr. Burbulis, "If you want to understand the mechanistic operation of biological systems, you need to know the precise numbers of each component part found in individual cells. Tadpoles and methods based on them should make that possible."  To count molecules so precisely, the researchers resorted to statistical methods sometimes used in high-energy physics.  The improved statistical techniques may be useful in other applications, such as management of therapy for HIV.    The work is funded by MSI's Alpha Project, its flagship effort to predict the future behavior of a prototype cellular system.  The Alpha project is funded by the National Institutes of Health's National Human Genome Research Institute.  In 2002, NHGRI named MSI a "Center of Excellence in Genomic Science," an acknowledgement of MSI's past and future research contributions in the field.   "This invention is almost a textbook example of how research into fundamental biology can spin off applications that might impact human health and safety in fairly short order," said Dr. Brent.     The invention is also described in an accompanying Nature Methods "News and Views" article by Dr. Garry Nolan , who wrote that tadpoles may be an "appealing system for researchers wanting a standardized, high-throughput, and accurate detection system for... just about anything." Nature Methods is a first-tier journal for new methods and significant improvements in life sciences and chemistry.

The Alpha Project Announces Broadly-Based Scientific Advisory Board

              Dr. Roger Brent, President and Director of Research at the Molecular Sciences Institute ("MSI"), announced today that seven distinguished scientists will serve on MSI's Alpha Project Scientific Board.

              The Alpha Project is an ambitious interdisciplinary effort to quantitatively examine communication within cells and develop computer models that accurately predict intra-cellular signaling. Gaining this level of understanding will require the development of new research methods and computational tools.  One future goal of this research is to distribute such methods and tools so that they can be used to study more complex systems such as human diseases.

               Members of the Board are Maynard Olson, Ph.D (chair), Richard Karp, Ph.D., Melissa Franklin, Ph.D., Daniel T. Gillespie, Ph.D., Natalie Ahn, Ph.D., Paul Sternberg, Ph.D. and Rebecca Ward, Ph.D.

The Molecular Sciences Institute Announces External Advisory Board  

Dr. Roger Brent, President and Director of Research at the Molecular Sciences Institute ("MSI"), announced the appointment of five distinguished scientists to its External Advisory Board.       The External Advisory Board will assess the scientific performance and progress of more than twenty researchers at MSI, and will offer advice and direction to the fellows as they pursue their scientific goals.    "MSI is an exceptional place for young researchers," said Dr. Brent. "We have created an environment to foster innovative scientific pursuits, without some of the constraints imposed by conventional academic or corporate organizations.  With the help of this extraordinary advisory board, we can push our research fellows to even higher levels -- and in so doing, nurture younger researchers prepared for the ambitious multidisciplinary projects that form part of the future for biology." 

Named to the External Advisory Board were Dr. Geoff Duyk, Dr. Nancy Hopkins, Dr. Alexander Johnson, Dr. Cynthia Kenyon, and Dr. Carl Pabo.   

Geoffrey M. Duyk, M.D., Ph.D., was most recently President of Research and Development and Chief Scientific Officer of Exelixis, Inc, where he had supervisory authority over a team of 500+ scientists.  He will chair the Board.   Prior to joining Exelixis, he was one of the founding scientific staff at Millenium Pharmaceuticals where he was responsible for building and leading the informatics, automation, DNA sequencing and genotyping groups.  Before that, Dr. Duyk was an Assistant Professor of Harvard Medical School in the Department of Genetics and Assistant Investigator of the Howard Hughes Medical Institute.  Dr. Duyk brings to the board an extraordinarily broad perspective on science in industry, universities, and government.

Nancy Hopkins, Ph.D., is the Amgen, Inc. Professor of Molecular Biology at Massachusetts Institute of Technology.   She holds a B.A. from Radcliffe College and a Ph.D. from Harvard University, where she worked directly with Mark Ptashne.  She was a postdoctoral fellow of James D. Watson at Harvard and the Cold Spring Harbor Lab and co-authored the fourth edition of a textbook, "The Molecular Biology of the Gene," with Watson and three colleagues.  Her early research moved from gene expression in bacteriophage lambda, to genetics of leukemogenic viruses. Later, after sabbatical work with Nusslein-Volhard, she developed a method of insertional mutagenesis for the zebrafish using retroviral vectors. Her lab used this method to identify and clone about 25% of the genes essential for development of the zebrafish larva.  As Co-Chair, with Provost Robert Brown, of the  Council on Faculty Diversity, she serves on the Academic Council of MIT. She chaired the committee that wrote the 1999 "MIT report" on the status of female faculty in science at MIT which lead to increased awareness of equity issues for women in science at MIT and other universities.  She is a fellow of the American Academy of Arts and Sciences and a member of the Institute of Medicine of the National Academy of Sciences where she serves on the Council of the IOM. 

Alexander ("Sandy") Johnson, Ph.D., is Professor and Vice Chair, Department of Microbiology & Immunology, and Professor, Department of Biochemistry & Biophysics, at The University of California, San Francisco.  He received a BA from Vanderbilt University.  He did his Ph.D. work with Mark Ptashne at Harvard and postdoctoral work with Ira Herskowitz at UCSF. His laboratory at UCSF studies transcriptional regulation, microbial pathogenesis, and evolution.  He is one of the authors of the textbook, "Molecular Biology of the Cell."  Among other strengths, Dr. Johnson brings to the board an encyclopedic understanding of contemporary molecular, cellular, and developmental biology. 

Cynthia Kenyon, Ph.D. is the Herbert Boyer Distinguished Professor of Biochemistry and Biophysics at the University of California, San Francisco.  Her undergraduate degree in chemistry and biochemistry is from the University of Georgia, Athens.  As a graduate student, she worked on the SOS response with Graham Walker at MIT and performed postdoctoral work with Dr. Sydney Brenner at the MRC Laboratory of Molecular Biology in Cambridge.  Her current research with C. elegans explores how genetic changes can allow these worms to live up to six times as long as normal.  She co-founded a company, Elixir, which is following paths to development of anti-aging therapies which come from her own work.  Among other strengths, she brings to the board the perspective gained from being an outstandingly successful and productive scientist.  She is a member of the American Academy of Arts and Sciences and of the US National Academy of Sciences and Medicine.

Carl O. Pabo, Ph.D. is currently a visiting faculty member in the Division of Biology at the California Institute of Technology.  He was Chief Scientific Officer of Sangamo BioSciences, and, before that, Professor of Biophysics and Structural Biology and Howard Hughes Medical Institute Investigator at the Massachusetts Institute of Technology.  As a graduate student and postdoctoral fellow at Harvard, Dr. Pabo solved one of the first structures for regulatory proteins, the DNA binding portion of phage lambda repressor. As a professor at the Johns Hopkins Medical School and then at MIT, Dr. Pabo contributed greatly to the understanding of the homeodomain and zinc finger DNA-binding proteins. He received his B.S. (summa cum laude) in Molecular Biophysics and Biochemistry from Yale College. Dr. Pabo thinks widely about biology, and brings to the board this extensive background as well as a great fund of knowledge and interest focused on organizational strategies and on developing the abilities of younger scientists. He is a member of the National Academy of Sciences and of the American Academy of Arts and Sciences. 

Dr. Roger Brent, Molecular Sciences Institute's President and Research Director, is honored with the Gabbay Award

Berkeley, CA - October 29, 2003 - Dr. Roger Brent, President and Research Director of the Molecular Sciences Institute, will receive the  Jacob Heskel Gabbay Award in Biotechnology and Medicine.   Dr. Brent shares the honor with Dr. Stanley Fields, Professor of Genome Sciences and Medicine at the University of Washington, Seattle.  Drs. Brent and Fields are being honored for their development of yeast two-hybrid and yeast mating interaction traps. The award recognizes people whose work had "outstanding scientific content and significant practical consequences in the biomedical sciences." As this year's honorees, they will each present their work at the "6th Annual Gabbay Award Lecture" at Brandeis University, held on October 30, 2003.   Dr. Brent is President and Research Director at MSI, an independent nonprofit research laboratory that combines genomic experimentation with computer modeling. The MSI mission is to predict the behavior of cells and organisms in response to defined genetic and environmental changes. Progress toward this goal will significantly increase our understanding of biological systems and help catalyze radical changes in how diseases are understood and treated.   In 2002, The National Human Genome Research Institute (NHGRI) of the National Institutes of Health named the Molecular Sciences Institute's Center for Genomic Experimentation and Computation one if its four Centers of Excellence in Genomic Sciences, an acknowledgement of MSI's past and future research contributions to the new field of predictive biology.   Prior to joining MSI, Dr. Brent was Associate Professor in the Department of Genetics at Harvard Medical School and Associate Researcher in the Department of Molecular Biology at Massachusetts General Hospital. He holds a B.A. in Computer Science and Mathematics from the University of Southern Mississippi and Ph.D. in Biochemistry and Molecular Biology from Harvard University.   He is known for his work on the modular structure of transcription regulatory proteins, his contributions to an understanding of gene and allele function based on protein interaction, and more recently for his work to develop experimental methods and computational frameworks that allow quantitative prediction of the future behavior of biological systems. He is a long time advisor on genomic and computational biology to corporations, private philanthropies, and the US government.

Dan Gillespie, revered mathematical chemist, joins MSI's efforts to model biological systems.          

              Dr. Roger Brent, President and Director of Research at the Molecular Sciences Institute ("MSI"), announced that Daniel Gillespie has agreed to work with MSI to explore computational simulations of intracellular biological processes.     Dr. Gillespie's efforts will be sponsored by MSI as part of its collaboration with Sandia National Laboratories' Genomes to Life (GTL).  GTL is a project funded by the Department of Energy, Office of Science.      Dr. Gillespie, a highly respected mathematical chemist, is a pioneer in stochastic methods for modeling chemical kinetics.  In 1976, in a widely-referenced paper, he described a stochastic simulation algorithm, a method to simulate an individual molecular reaction.  This method is the basis for many practical simulations today.   His expertise will be particularly important to MSI and Sandia, as they jointly explore complex simulations of intracellular biological processes.  Specifically, Dr. Gillespie will work towards coupling exact discrete reaction event simulators with continuous numerical integration networks.  Such hybrid networks are a necessary part of the numerical tool kit for studying systems composed of coupled biochemical reactions.   In keeping with MSI's long-standing tradition of conducting research that benefits society, computational methods developed from this project will be made publicly available.

Towards an Anthropology of Biology:  Genomics and Citizenship :  CGEC course debuts at the University of California, Berkeley          

      MSI Research Director, Dr. Roger Brent, will teach an important and timely course at the University of California, Berkeley, geared toward understanding the science and societal impacts of genomics.     The course, "Towards an Anthropology of Biology: Genomics and Citizenship" (LNS 126), is part of a series of prestigious multidisciplinary offerings from the UC Berkeley College of Letters and Sciences, which fosters the ideals of a liberal arts education at the highest levels of excellence.  The course will provide an overview of the most pressing issues in genomic biology, the world in which genomic biology functions, and the world that it has shaped.   Dr. Roger Brent, a molecular biologist, will co-teach this course with Dr. Paul Rabinow, an anthropologist and Professor of Anthropology at the University of California, Berkeley.   

Dr. Brent is President and Research Director at the Molecular Sciences Institute, an independent, non-profit research laboratory that combines genomic experimentation and computer modeling.  The MSI's Center for Genomic Experimentation and Computation (CGEC) is a $20 million effort led by Dr. Brent to study and model the quantitative behavior of a cellular signal transduction and protein regulatory network.  The MSI Center includes members from four other institutions:  MIT, Caltech, UC Berkeley and Pacific Northwest National Laboratory.  In 2002, the MSI Center was named a Center of Excellence in Genomic Sciences by the National Human Genome Research Institute, part of the National Institutes of Health.         

Dr. Rabinow is a distinguished cultural anthropologist and pioneer of using ethnographic techniques to study Western civilization.  He is a respected scholar of Michel Foucault and editor of the English translation of Foucault's work.  Throughout his career, Dr. Rabinow has been particularly interested in the workings of science.  To that end, he authored "Making PCR," the widely-read account of Cetus Corporation's invention of one of the most significant biotech discoveries of our time - the polymerase chain reaction, and "French DNA: Trouble in Purgatory," which details the story of when a French-American research collaboration was stymied because of issues surrounding the use of genetic material collected from French families.   This highly novel and experimental course, an official activity of the CGEC, is being offered at the cross-section of anthropology and biology because humanity is constantly reshaped by revolutions in the life sciences.  At its core, the course will consider whether humankind is currently crossing a threshold where biology will affect human self-understanding as powerfully as did the Darwinian synthesis.   Its lofty goal is to provide students the analytical framework they need in order to participate fully in the debate that democratic societies will continue to have on these issues.    Classes are Tuesdays and Thursdays at 2:00 pm from August 26 to December 4 in Room A of the Hearst Annex Building.   The course syllabus and reading assignments are listed on the MSI website.   

General information about the course is also available at the UC Berkeley website. The Molecular Sciences Institute is an independent nonprofit research laboratory that combines genomic experimentation with computer modeling. The MSI mission is to predict the behavior of cells and organisms in response to defined genetic and environmental changes. Progress toward this goal will significantly increase our understanding of biological systems and help catalyze radical changes in how diseases are understood and treated.

MONOD Adds Features, Developers and Momentum       

Berkeley, CA - April 10, 2003 - The Molecular Sciences Institute today released an enhanced version of software that enables collaborative biological research and added two bioinformatics fellows, Kirindi Choi and Jay S. Doane, to the development team. 

The software, known as MONOD, for MOdeller's NOtebook and Datastore, is designed to help researchers work together seamlessly to construct computer models of biological systems.  MONOD allows teams of researchers to store and structure the information they need to build these models, from journal articles to individual pieces of laboratory data, in a way that is accessible on the Internet.

    The revised version released today incorporates a number of new features.  It allows for integrated PDF downloading and provides a much easier installation process.  It has greatly improved abilities to search for relevant articles on the bibliographical database PubMed.  It supports multiple nomenclatures for proteins, and automatically establishes links to external databases.  Both user and group administration controls are included, as well as revision control and permission control.  Finally, the user's view of the entire database can be filtered by date range and keyword.

Initial development of MONOD  was funded by the Defense Advanced Research Agency.  The improvements released today were written by David Soergel, a computer science research fellow at MSI.   Kirindi Choi and Jay S. Doane now join David on the team developing MONOD.  

Kirindi Choi has over 17 years of experience in the software arena.  During that time, she played an instrumental role in the development of gene expression, proteomics and genomics commercial software.  She received a Bioinformatics Certificate from Stanford University, and a BA in Applied Mathematics from the University of California, Berkeley.   

Jay S. Doane is an expert in object oriented and component architectures.  He has over 7 years experience conducting object/component oriented analysis, design, development, and methodologies, focusing on secure, persistent, concurrent, distributed systems.  He received an M.S. and Ph.D. in Astronomy and Astrophysics, and a B.A. in Physics from the University of California, Santa Cruz.

Software such as MONOD is important because it supports several emerging trends in the biological sciences.  First, many biological problems can no longer be solved by individual scientists.  Biologists are eager to create "laboratories without walls", so that they can be linked to their colleagues, databases, remote supercomputers, and scientific instruments.  Second, researchers at MSI and other leading institutions believe that biology needs to become a more predictive and quantitative science.  This will require a tight feedback between experimental work and modeling and simulation, which MONOD is designed to support. In keeping with the Institute's mission to perform research that benefits the public, MONOD is Open Source and is freely downloadable from  http://monod.molsci.org .  It is licensed under the Lesser GNU Public License.  The "open source" model also allows users from around the world to fix "bugs" and contribute or suggest new features.

"MONOD provides a comprehensive framework to allow scientists to structure and make sense out of a massive amount of data," said Dr. Roger Brent, Director of the Molecular Sciences Institute.  "MSI is delighted to make these enhancements available to researchers worldwide."

MONOD is one of the first useful outcomes of the Alpha Project, a multidisciplinary effort to predict the quantitative behavior of a single cellular information processing system.  This work is funded by a multi-million dollar grant from the National Human Genome Research Institute.

Sydney Brenner receives the Nobel Prize in Stockholm today    

The Molecular Science Institute Awarded its First United States Patent                

              Dr. Roger Brent, President and Director of Research at The Molecular Sciences Institute (MSI), announced that MSI has been awarded a patent for a unique method for characterizing protein molecules.     The patent, "Protein Fingerprint System and Related Methods", aka "Fluorescence Fingerprinting," is a way to identify proteins based on their physical properties, which are calculable from the genome.  By attaching different kinds of detectable tags to different amino acids, the numbers of those amino acids within a protein may be determined. Inventors Ian Burbulis and Robert Carlson were named with Brent on the award, United States Patent No: US 6,569,685 B1.

              Dr. Burbulis, a Research Fellow at MSI, is an expert in biochemistry and proteomics. Dr. Carlson, a former Research Fellow at MSI, is now part of the Electrical Engineering Department at the University of Washington in Seattle.     

              "The Molecular Science Institute performs its research in the interest of the public good," said Dr. Brent.  "This will be in the forefront of our minds as we work toward developing this technology."  The method described in the patent provides a way to differentiate between protein species in a sample by turning sequence information into physically measurable characteristics.   More specifically, a protein molecule of interest is isolated from other types of protein molecules.  The protein molecule of interest is modified to a one-dimensional structure from the natural three-dimensional structure of the protein molecule.  Each of a first type of amino acid residue of the protein molecule is labeled with a first tag.  Each of a second type of amino acid residue of a protein molecule is labeled with a second tag.  The first and second tags impart to the protein molecule a detectable set of characteristic ancillary properties that facilitates distinction of the protein molecule of interest from other types of protein molecules.  When these ancillary properties are detected, a fingerprint of the protein molecule is revealed.  A listing of known protein molecules and of the fingerprints corresponding to each of the known protein molecules serves as a library to facilitate identification of unknown proteins. A fingerprint of a protein molecule of interest determined in the same manner as the fingerprints of known proteins listed in the library is compared with fingerprints of the known protein molecules to identify the protein molecule of interest.  The Molecular Sciences Institute is an independent nonprofit research laboratory that combines genomic experimentation with computer modeling. The MSI mission is to predict the behavior of cells and organisms in response to defined genetic and environmental changes. Progress toward this goal will significantly increase our understanding of biological systems and help catalyze radical changes in how diseases are understood and treated.

The Molecular Sciences Institute's "Alpha Project" supports Systems Biology Markup Language

The Molecular Sciences Institute ("MSI") announced today that Andrew Finney, one of the chief architects of Systems Biology Markup Language (SBML), will join The Alpha Project as a consortium member.

              The Alpha Project is the flagship activity of MSI's Center for Genomic Experimentation and Computation ("CGEC"), a $20 million effort to study and model the quantitative behavior of a cellular signal transduction and protein regulatory network.    Dr. Finney and his team will join the CGEC collaborators, led by MSI, which include researchers from the California Institute of Technology, the Massachusetts Institute of Technology, the University of California, Berkeley, and Pacific Northwest National Laboratory.   In 2002, CGEC was named a "Center of Excellence in Genomic Sciences" by the National Human Genome Research Institute, part of the National Institutes of Health.  The Alpha Project's goal is to predict the flow and processing of information within cells in a prototypical pathway, the pheromone signal transduction pathway in baker's yeast (Saccharomyces cerevisiae). Though a simple organism, yeast cells have much in common with cells of more complex organisms, including humans.   Quantifying how cells sense and respond to various stimuli and creating a model that will accurately predict these responses are the first important steps to understanding diseases and eventually to tailoring precise treatments to each individual. Gaining this level of understanding will require the development of new research methods and computational tools to probe and analyze such complex biological processes.   Dr. Finney, a Research Fellow in the BioComputation Group in the Science and Technology Research Centre at the University of Hertfordshire in the UK, will work with MSI to develop computational methods to simulate the signal transduction pathway.   This effort will build on Dr. Finney's work on one of the most fundamental problems faced by computational biologists -- that simulation models and results often cannot be compared or shared because the models and methods developed by researchers at different laboratories are usually not compatible with each other.  Dr. Finney's group began to address this problem by developing SBML, an open, extensible, model representation language that facilitates collaboration among developers of systems biology software.  In keeping with MSI's mission to perform research that benefits the public, the results of Dr. Finney's work on the Alpha Project, will be licensed under the Lesser GNU Public License, and be freely downloadable. 

Sydney Brenner, Molecular Sciences founder, is awarded the Nobel Prize     

                The Nobel Prize in Physiology or Medicine for 2002 has been awarded to Molecular Sciences Institute founder, Dr. Sydney Brenner.  Dr. Brenner shares the honor with former colleagues Dr. H. Robert Horvitz at MIT and Dr. John E. Sulston at the Wellcome Trust Sanger Institute in Cambridge, England.

              The prize to these three investigators was awarded for their work on the nematode (roundworm), Caenorhabditis  elegans. A simple animal with very few cells, it has many of the functions found in higher organisms.  It moves, it eats, it senses its environment, it ages.  Study of these processes in the worm has revealed genes that control the same processes in humans.

              Dr. Brenner articulated the case for development of C. elegans as a desirable object of study (or "model system") in 1963.  By turning the worm into a workable experimental animal, and by evangelizing about the possible discoveries that researchers working on it might make, Sydney attracted and helped guide the formation of dozens of younger researchers who developed the field. Sulston and Horvitz were among the earliest and most accomplished of these disciples.

              Sydney's contributions to science now span almost five decades. The work on worms, which the prize honors, is only one of his important achievements.

Additional Contributions to Biology

Beginning in the 1950s, Sydney contributed to the development of molecular biology, in particular with seminal contributions to the elucidation of the genetic code and the identification of mRNA. He also made great contributions to the understanding of antibody diversity. During the 1980s and 1990s, he was one of the people most responsible for the genome sequencing projects and the information that they produced.

       It was in part the success of these sequencing projects, together with the molecular biological enterprise that he had helped to launch, that led him to promote systems biology and create the Molecular Sciences Institute. In this endeavor, scientists from many disciplines study how individual genes and proteins work together to create system outcomes. The work at the Molecular Sciences Institute is an ongoing tribute to another contribution by this remarkable scientist.

Background

Born in Germiston, South Africa on January 13, 1927, Sydney received his bachelors and masters degrees from the University of Witwatersrand, South Africa (1947 and 1951, respectively).  He went on to pursue D. Phil. Studies at Oxford University, England (1954).  He has been married to May Brenner for 50 years and they have 4 children.

      Among Sydney's many honors are the 1974 Royal Medal and the 1991 Copley Medal of the Royal Society of London, two Albert Lasker Awards, (for Medical Research in 1974 and for Special Achievement in Medical Science in 2000), the 1991 Gairdner Foundation International Award, the 2002 March of Dimes Prize in Developmental Biology, and the 2002 Dan David Prize. Sydney is a Fellow of King's College and the Royal Society.  He has honorary memberships in numerous other societies and honorary degrees in over two dozen colleges and universities worldwide.  He founded the Molecular Sciences Institute in 1996.

The MSI Appoints Roger Brent President and Chief Executive Officer                

              The Molecular Sciences Institute Board of Trustees has appointed Dr. Roger Brent, President and Chief Executive Officer at its July 23, 2001 Board meeting."I am deeply grateful for this vote of confidence by the members of the Institute Board of Trustees," said Brent. "At the Institute, we need to continue the ongoing program of functional genomic experimentation and development of computational methods. We need to learn how sets of genes work together to create system outcomes, and we need to learn for the world how to conduct multidisciplinary research on biological problems. This is a big job but success would have a large upside and we have the right people to do it."

"I began the Institute with the hope of establishing a place where innovative research could be pursued across the boundaries of the many disciplines that constitute modern biology," said Sydney Brenner, Ph.D., founder and former President and Research Director of the Molecular Sciences Institute. "My research interests in applying computational theory to biological processes in the fields of genetics and evolution were strongly complemented when Roger joined the Institute and brought his interests in the areas of the regulation of gene expression and signal transduction. The Institute has been successful in attracting a group of talented young scientists who will, under Roger's leadership, continue to build this research in the future."

              Roger Brent, Ph.D., joined the Molecular Sciences Institute as Associate Director in December of 1997 and was appointed Director in January 2001. In both capacities, he played a major role in establishing the presence of the Institute in the Bay Area, and particularly in shaping the current scientific vision for the Institute. He was also appointed Adjunct Professor at UCSF in 2000. Prior to joining the Institute, Brent was Associate Professor in the Department of Genetics at Harvard Medical School and Associate Researcher in the Department of Molecular Biology at Massachusetts General Hospital. He holds a B.A. in Computer Science and Mathematics from the University of Southern Mississippi and Ph.D. in Biochemistry and Molecular Biology from Harvard University.

Brent is known for his work on the modular structure of transcription regulatory proteins, his contributions to an understanding of gene and allele function based on protein interaction, and more recently for his work to develop experimental methods and computational frameworks that allow quantitative prediction of the future behavior of biological systems. Before helping start the Institute in Berkeley, he was at Harvard for 25 years. He is a long time advisor on genomic and computational biology to corporations, private philanthropies, and the US government.

              "Roger is a world-class scientific researcher and I am excited to have him lead the vision he and Sydney established for the Institute," said Bill Murray, one of the founding members of the Board of Trustees. "He has been extremely successful in attracting research funding to support the ongoing operations of the Institute and has also been successfully recruiting bright, young scientists to contribute to its future."

              "I have much faith that Roger will lead the Institute well," said Gunter Blobel, founding member of the Board of Trustees and recipient of the Nobel Prize in Physiology or Medicine in 2000. "I am highly supportive of Roger in his new leadership role."

MSI Announces its "Genomic Sciences Summer 2005 Internship" for High School Juniors and Seniors

              The Molecular Sciences Institute in Berkeley, CA is pleased to announce that Applications and Recommendation Forms are available for its Third Annual Genomic Sciences Summer Internship Program.  The Molecular Sciences Institute is committed to training, motivating and mentoring future genomic scientists.  Our Genomic Sciences Internship Program provides Bay Area high school juniors and seniors an exceptional opportunity to gain hands-on experience in a genomics laboratory for eight weeks each summer.  These competitive internships are sponsored by the National Human Genome Research Institute. MSI combines genomic experimentation with computer modeling. The mission of MSI is to predict the behavior of cells and organisms in response to defined genetic and environmental changes.  Progress toward this goal will significantly increase our understanding of biological systems and help catalyze radical changes in how diseases are understood and treated.    These 8-week internships are open to students who are high school juniors or seniors during the 2004-2005 academic year.  After receiving a comprehensive introduction to genomics at MSI, students will select a research area and partner with an MSI scientist to complete a research project, written report, and oral presentation.  Eighty percent of a student's time will be spent at MSI doing research, learning about the backgrounds of our collaborators during "Meet the Scientists" presentations, participating in genomics workshops and a journal club, and attending MSI team meetings.   Twenty percent of a student's time will be spent on MSI-sponsored scientific enrichment activities and fieldtrips throughout the Bay Area to supplement the student's learning.  To learn about MSI interns from the Summer 2003 and the Summer 2004,please visit their web pages. Interns will receive a stipend of $500 per week.  After completing the summer internship, students may also take advantage of ongoing individualized tutoring in science and mathematics provided by MSI throughout the following school year.  In addition, MSI will pay for an SAT preparation course for the student.    Interns must be U.S. citizens or permanent residents.  

MSI Announces Changes to Board of Trustees          

The Molecular Sciences Institute today announced the appointment of two new members to the nonprofit corporation's Board of Trustees: Charles Cantor, Ph.D., Chief Scientific Officer at Sequenom, Inc., a biotechnology company, and Denise Caruso, Executive Director of the Hybrid Vigor Institute, a nonprofit that seeks to promote the conduct of interdisciplinary research.

      Charles Cantor brings to the Molecular Sciences Institute a wealth of experience in biological technologies and genomic biology," said Roger Brent, Ph.D., President and Research Director of the Molecular Sciences Institute.  "He has played a key role in public sector genome efforts and in building a research organization that can understand the consequences of human genetic variation. We look forward to a long future working together to grow the Institute."

      Dr. Charles Cantor is Chairman of Sequenom, Inc.'s Scientific Advisory Board and was appointed Chief Scientific Officer in June 1998.  Sequenom, in La Jolla, California is developing technology to analyze single nucleotide polymorphisms (SNPs).  Understanding of SNPs is expected to play an essential role in the future of drug development, diagnostics and other life science applications.  These variations represent the origin of most differences between individuals, including predisposition to disease, drug tolerance and drug efficacy.  Dr. Cantor was previously the chair and professor of the department of biomedical engineering and biophysics, and director of the Center for Advanced Biotechnology at Boston University.  Prior to this Dr. Cantor held positions at Columbia University.  He was also director of the Human Genome Center Project of the Department of Energy at Lawrence Berkeley Laboratory.  Dr. Cantor is a consultant to more than 16 biotech firms, has published more than 325 peer reviewed articles, been granted 26 US patents, and co-authored a three-volume textbook on Biophysical Chemistry. He recently completed the first textbook on Genomics: The Science and Technology of the Human Genome Project.

              Denise Caruso is founder and executive director of the Hybrid Vigor Institute in San Francisco, California, whose mission is to deploy the methods of interdisciplinary research to solve complex social, cultural and scientific problems related to the environment, human health and developments in biotechnology. A veteran journalist and technology analyst, Caruso has for nearly 20 years chronicled the intersection of digital technology, telecommunications and interactive media.  From October 1995 until April 2000, she wrote the Technology column for the Monday New York Times.  In January 2000, Ms. Caruso became an occasional contributor to The New York Times' Arts & Ideas section, writing primarily about scientific and academic research in progress. She was an early advocate of First Amendment rights in cyberspace, and one of the first journalists to focus on the intersection of technology, commerce and culture.  She has served on the board of directors of the Electronic Frontier Foundation, and as an advisor to the Center for Public Knowledge.

              "Denise is a knowledgeable and tireless advocate for understanding the broader implications of technological progress," said Brent.  "She brings invaluable expertise in interacting with the technology industry, and her perspective embraces interdisciplinary work as critical to the acceptance of the results of genomic biology into the mainstream of the global economy and culture."

MSI Evolution Project Funded by the National Science Foundation                     

The Molecular Sciences Institute announced that a significant grant to study genomic evolution in yeast has been awarded from the National Science Foundation (NSF).  The $390K grant, under the direction of Dr. Evgeny Kroll,  will fund a two-year project focused on understanding how organisms rearrange their genomes (sometimes exchanging pieces of entire chromosomes) in response to changes in their environment.

The biological importance of these genome rearrangements lies in the fact that they can apparently be induced by stresses in the environment.  Otherwise-identical organisms with different genomes cannot make fertile offspring and thus can branch to form separate species.  It is possible that the current stresses in the global environment, such as global warming, are speeding up evolution and the creation of new species

We now know that the rates of other kinds of genetic change, and thus of evolution, are controlled by the environment.  Now it appears that the rate of speciation might also be under environmental control as well.  I hope that this study will illuminate mechanisms that have remained without experimental or even much theoretical support since the framework was laid by Darwin," sais Dr. Kroll.

Dr. Roger Brent, Research Director at the Molecular Sciences Institute, points out that, "It was only recently that we understood that the rate of evolution might be under genetic control, how that system could respond to changes in the environment.  In the 1980s we began to understand the mechanisms that allowed genetic and environmental control of the rate of point mutation.  A few years ago, researchers demonstrated a mechanism by which genetic and environmental changes can influence the frequency and degree of variation in body plan in fruit flies due to point mutations.   Kroll's work has shown that another kind of variation, variation in genome structure that often define speciation, is also under environmental control, and we can expect he will find the genes that govern that process as well.  This is an important project."

This grant will be the first for Dr. Kroll as an independent investigator and the first NSF grant to the Institute.  "I am grateful to the NSF for the opportunity to try to discover basic molecular mechanisms that govern evolution and species formation." Dr. Kroll said.

MSI and DARPA forge new tool for collaborative bioresearch

              The Molecular Sciences Institute today released software to enable collaborative biological research.  The software is called MONOD, for MOdeller's NOtebook and Datastore.  MONOD is designed to help researchers work together to construct computer models of biological systems.  Construction of such models is one of the major enterprises facing biologists in the 21st century, and it is clear that these models will be constructed and tested by multidisciplinary research teams.  MONOD allows teams of researchers to store and structure the information they need to build these models, from journal articles to individual pieces of laboratory data, in a way that is accessible on the web. As a result, researchers can use MONOD to manipulate these data structures from anywhere in the world, as well as to interact with one another.

              Initial development of MONOD was funded by the Defense Advanced Research Agency (DARPA) Information Processing Technology Office.  Its name is intended to evoke the memory of Jacques Monod, the great French biologist who, with Francois Jacob, developed among the first molecular models of biological systems, for which they were awarded the Nobel Prize in 1962.

              The MONOD project was spearheaded by Dr. Drew Endy, a Research Fellow at the MSI when the project began, now a Fellow in Biology and Bioengineering at MIT.  Said Endy, "Not all researchers who want to build models of biological systems are disposed to read and make sense of the oftentimes internally inconsistent data found in the biological literature.  MONOD structures biological knowledge at a level between the English language of a scientific paper and the systems of equations in the actual model.  By using MONOD, one does part of the structuring of the model up front.  Furthermore, the process of model 'capture' can be distributed across an entire community of users, from primary experimentalists, to modelers, to analysts."

              Monod was written by David Soergel, computer science Research Fellow at the MSI, with help from Brian George, a longtime friend and coworker.  It was written exclusively with Open Source tools: Java Servlets, the Resin servlet engine, the PostgreSQL database engine, and an application framework previously developed by Soergel and George.                "MONOD helped a researcher at the MSI conceive a potentially important experiment  on their first day of using the system.  It's gratifying that the software we've written is having an immediate impact on furthering basic biological research," said Mr. Soergel.                "MONOD is a major step in enabling biology researchers and analysts to structure the massive amounts of data that is becoming available, link it to the comparative study of alternate models of cell processes, thus enabling design of informed experiments and predictive biology. Soergel, Endy, and others at MSI have created, in a short span of time, an extensible framework to for such analysis," said Dr. Sri Kumar, Program Manager at DARPA.

              In keeping with the Institute's mission to perform research that benefits the public, MONOD is Open Source and freely downloadable from http://monod.molsci..org.  It is licensed under the Lesser GNU Public License (LGPL).

              MONOD has already been useful at the Institute in the construction of the quantitative model that underpins the Alpha Project, a five-year, $15M Institute-led effort to predict the quantitative behavior of a single cellular information processing system.   Work on the Alpha Project , which also involves labs at MIT, Caltech, UC Berkeley, and Pacific Northwest National Laboratory, is being funded by the National Human Genome Research Institute.  Says Dr. Roger Brent, Director of the Molecular Sciences Institute, "DARPA funding allowed us to develop MONOD and jump start work on the Alpha Project, for which we are thankful, and we are delighted to make this early milestone available to researchers worldwide."  <p>The Molecular Sciences Institute is an independent, nonprofit research laboratory that combines genomic experimentation with computer modeling. The MSI mission is to predict the behavior of cells and organisms in response to defined genetic and environmental changes.  Progress toward this goal will significantly increase human understanding of biological systems and help catalyze radical changes in how diseases are understood and treated.

Researchers Link Cell Proliferation to Cell Death

              The Molecular Sciences Institute announced that a group led by Dr. Andrew Mendelsohn has discovered that a protein required for cell proliferation and growth connects that regulatory system with the system that causes cell death.  The work was published today in the journal Proceedings of the National Academy of Sciences (PNAS).

The cell proliferation protein, Cyclin D3 sensitizes the cells to the cell death protein, Caspase  2.   The cell cycle system proteins govern cell division and are frequently altered in cancers.  The cell death regulatory proteins govern apoptosis, or "programmed cell death", which causes cells to commit suicide during normal human development (for example in the immune system) and which acts inappropriately in many human diseases (for example, in Alzheimer's).  Dr. Mendelsohn's findings represent the first physical and functional connection between these processes.

              "These findings are consistent with the idea that cell death may represent a last ditch system to cause cancerous cells to suicide rather than proliferate and cause a tumor," said Dr. Mendelsohn.

              The results depended on the development of a new method to test the importance of the protein-protein connection.  This method, which combines several commonly-used, high-tech lab techniques, will likely be practiced extensively by researchers who wish to discover other protein connections, including those in human disease.   Said Dr. Roger Brent, Research Director of the Molecular Sciences Institute and a member of the scientific team that performed the work, "For the MSI to accomplish its mission of predicting cellular behavior, we need to attack the problem of how cells work at all levels, which means we need to continue to develop means to identify proteins and protein-protein connections even for processes that we understand fairly well."

MSI Chosen as a Center of Excellence in Genomic Sciences by the National Institutes of Health and Awarded a $15.5M Grant for the Alpha Project             

The National Human Genome Research Institute (NHGRI) of the National Institutes of Health has awarded the Molecular Sciences Institute a $15.5 million, 5-year grant supporting MSI's Center for Genomic Experimentation and Computation (CGEC).  The federal government also named CGEC one of its four Centers of Excellence in Genomic Sciences, an acknowledgement of the MSI's past and future research contributions to the new field of predictive biology. MSI, a nonprofit research laboratory that combines genomic experimentation with computer modeling, is the first independent research institute to be recognized as a Center of Excellence under this program.   "The Center of Excellence in Genomic Sciences program brings together teams of investigators from different disciplines to encourage innovation and lay the groundwork for new genomics approaches to the study of human biology and disease," said Francis S. Collins, M.D., Ph.D., director of the National Human Genome Research Institute. "The NHGRI fosters these extraordinary collaborations because we believe they will produce important but unpredictable insights into genomics."    

              The grant supports MSI's Alpha Project, an ambitious effort to examine communication within cells and to develop computer models that accurately predict intra-cellular signaling. One ultimate goal of this research is to reveal insights that enable much more precisely targeted treatments for diseases.  "The Human Genome Project has shown us what proteins are encoded by the genome, but we still don't know very much about how individual proteins within cells interact with each other to cause diseases or other complex outcomes. Our work aims to understand this choreography so that we can predict the results of cellular changes, and ultimately, how certain changes contribute to disease," says Roger Brent, Ph.D., scientific director and president of MSI.  "Unique, interdisciplinary approaches to large scale scientific research like the Alpha Project will enable us to better understand human biology and cellular function," said J. Craig Venter, Ph.D., president of The Center for the Advancement of Genomics.  "It is encouraging to see that the innovative ideas of Dr. Brent and others at the Molecular Sciences Institute are being recognized and awarded significant federal funding to further their crucial research."  The Alpha Project's focus is on the flow and processing of information within cells in a prototypical pathway, the pheromone signal transduction pathway in a well studied, single cell organism, baker's yeast (Saccharomyces cerevisiae). Though a simple organism, yeast cells have much in common with cells of more complex organisms, including humans.   By developing and applying innovative experimental and computational approaches to this system, MSI scientists will generate an interactive model of the pathway. The Alpha Project, the research methods and the computer models developed are a pilot study to explore similar pathways in higher organisms.   The key to crafting predictive models will be the development of new research methods and computational tools to probe and analyze complex biological processes. MSI was established to enable and encourage collaboration among scientific disciplines to foster independent thinking and novel approaches so that these new research methods and computational tools will emerge.  Led by Brent at MSI, the Alpha Project brings together 40 independent researchers, faculty, postdoctoral fellows, and graduate students from a variety of fields including biology, chemistry, engineering, mathematics, computer science, and physics at the Molecular Sciences Institute, the California Institute of Technology (CalTech), the Massachusetts Institute of Technology (MIT), and Pacific Northwest National Laboratory.  As an independent, non-profit research laboratory, MSI practices the open publication and release of data, methods, and materials.  Similarly, the CGEC's work will be freely shared, so that its scientific achievements and new technologies can be disseminated quickly to scientists worldwide for maximum public benefit.  "We are eager to develop and test an 'open source biology' approach," says Brent. "This means that in appropriate situations we will go beyond the standard scientific practices of open publication and data release, to distribution of materials and technologies under open source licensing schemes."    

              Brent believes that open source licensing of new discoveries may be an effective way to take  findings from the Human Genome Project and the Alpha Project and bring about tangible impacts on agriculture, drug discovery, and ultimately, human health.  Founded in 1996 by Sydney Brenner and based in an 8,000-square foot laboratory in Berkeley, Calif., MSI has pioneered the concept of a biology-driven, multidisciplinary research institute attempting to predict the consequences of biological changes. MSI investigators have published scientific publications in journals such as Cell, Nature, and the Proceedings of the National Academy of Sciences.  "I'm delighted by this award, which recognizes MSI's contribution to this now rapidly developing field of biology which fuses the experimental with the computational approach," says Sydney Brenner, D.Phil.  "It will also allow MSI to develop its work further and enhance its ability to continue to attract young scientists to the field."  In addition to the new NHGRI funding, MSI is supported by other federal grants from the National Institutes of Health, the National Science Foundation and the Defense Advanced Research Projects Agency (DARPA), and from philanthropic contributions. Further information is available at http://www.molsci.org.

Researchers Discover Why Fate of Daughter Yeast Cell Differs From Its Mother; Early Milestone For Understanding How Single Cells Work     

Research Of Single Cells Promises Medical and Engineering Rewards If Successful       

       Even though a "mother" and "daughter" cell are endowed with the same genetic make-up, researchers have discovered genetic programs that make daughter cells very different from their mothers. The discovery, published this week as the cover article of the journal Cell, is a milestone in understanding how single cells process information and make decisions, that could lead in time to radical changes in how to target cells with medicines or manipulate organisms for better use in agriculture, according to researchers at the Molecular Sciences Institute (MSI), Berkeley.

          The MSI researchers looked at one of the simplest cases with brewer's yeast, in which a mother "buds" to give rise to a smaller daughter. "Although the two cells have the same genetic makeup, and see the same external world, they are quite different, and respond to the external environment in different ways, and do different things," said Dr. Alejandro Colman-Lerner, lead researcher on the study. Dr. Colman-Lerner performed the work along with Ms. Tina Chin.

              The change in the daughter cells begins before the daughter separates from the mother cells, according to the research. The mother cells pass specialized proteins through the neck before the daughter separates from the cell. The proteins help the daughter cell turn on genetic programs that cause the daughter to dissolve the ties to the mother cell. Both mother and daughter cells are left with scars, and differences in the decisions they make thereafter.

              "Before this work, a great deal was known about how mothers came to be different from their daughters, but what this work shows is the other half of the story - that the daughter comes to be different by her own actions," said Dr. Roger Brent, MSI Director of Research.

              Dr. Brent and his team are part of a larger contingent of West Coast researchers who are working on the Alpha Project, a five-year program whose goal is to allow the computational prediction of the precise behavior of single cells in response to defined changes in their external and internal environments.

              "Alejandro's work is an important early milestone in the Alpha project," Dr. Brent said. "The Alpha Project could profoundly increase the human understanding of living systems. In the long term, if the project is successful, results could lead to different and better approaches to drug development and result in therapies that use lower dosages and produce fewer side effects. And in the world of agriculture, we might have a better ability to engineer plants and animals."

              For example, today, researchers at a biotech or pharmaceutical company who make a drug will typically identify a single protein molecule involved in a disease. They then attempt to discover molecules that keep the target protein from working. To be effective as drugs, the molecules need to bind the target protein tightly, stop it from working, and have little or no effect on other protein molecules to avoid causing side effects. If this week's milestone is an indication, and the project achieves its ultimate goal, researchers could make models that may make it easier to find effective drugs.