News and Events
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.
Abstract: One goal of systems biology is to understand how genome-encoded parts interact to produce
quantitative phenotypes. The Alpha Project is a medium-scale, interdisciplinary systems biology effort that aims to achieve this goal by understanding fundamental quantitative behaviors of a prototypic signal transduction pathway, the yeast pheromone response system from Saccharomyces cerevisiae. The Alpha Project distinguishes itself from many other systems biology projects by studying a tightly bounded and well-characterized system that is easily modified by genetic means, and by focusing on deep understanding of a discrete number of important and accessible quantitative behaviors. During the project, the authors have developed tools to measure the appropriate data and develop models at appropriate levels of detail to study a number of these quantitative behaviors. The authors have also developed transportable experimental tools and conceptual frameworks for understanding other signaling systems. In particular, the authors have begun to interpret system behaviors and their underlying molecular mechanisms through the lens of information transmission, a principal function of signaling systems. The Alpha Project demonstrates that interdisciplinary studies that identify key quantitative behaviors and measure important quantities, in the context of well articulated abstractions of system function and appropriate analytical frameworks, can lead to deeper biological understanding. The authors’ experience may provide a productive template for systems biology investigations of other cellular systems.[ PDF]
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 [PDF] ), 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 download PDF]
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[PDF];Tsong, et.al. 2006 [PDF] 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 albicans to 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. |