CSB2: Council for Systems Biology in Boston
CSB2 News
Registration now open for International Conference on Systems Biology of Human Disease
Published March 31, 2010
Register now for the Systems Biology of Human Disease conference, June 16–18 2010
CCC2010 poster prize winners announced
Published February 2, 2010
CSB2 is happy to announce that Melanie Müller from the Harvard Physics Department and Kenneth Evan Thompson from the MIT Biology Department won the two poster prizes at CCC2010. Each recipient will receive a $200 award, funded by the Center for Modular Biology under NIH grant NIGMS68763. The abstracts of their poster presentations follow:
#19 Intracellular cargo transport: Molecular motors playing tug and tug-of-war
Melanie J.I. Müller1,2, Florian Berger2, Stefan Klumpp2, Reinhard Lipowsky2
1Department of Physics, Harvard University, 2Max Planck Institute for Colloids and Interfaces
Intracellular transport is based on molecular motors that pull cargos along cytoskeletal filaments. Kinesin and dynein motors walk along microtubule filaments, while myosin motors move along actin filaments. One motor species walks actively only into one direction along the filament, e.g. kinesin-1 moves to the microtubule plus-end, whereas cytoplasmic dynein moves to the microtubule minus-end. However, many cellular cargos are observed to move bidirectionally, involving both plus- and minus-end-directed motors. The presumably simplest mechanism for such bidirectional transport is provided by a tug-of-war between the two motor species. We have studied this mechanism theoretically, using the load-dependent transport properties of individual motors as measured in single-molecule experiments. In contrast to previous expectations, such a tug-of-war is found to be highly cooperative and can lead to fast bidirectional motion with or without pauses, as observed in vivo. Our model reproduces experimental results on bidirectional transport of lipid droplets in Drosophila embryos, which have previously been thought to be incompatible with a tug-of-war scenario. One motor species walks actively only along one type of filament. However, the motor myosin-5, which walks actively along actin filaments, can passively diffuse along microtubules. Cargos that are transported along a microtubule by one kinesin and one myosin motor exhibit interspersed moving and diffusing events and increased processivity. We explain this behavior by a stochastic tug model similar to the tug-of-war model.
#23 Heterospecific modules for molecular engineering identified from a synthetic coiled-coil interactome
Kenneth Evan Thompson, Aaron Reinke, Robert Grant, Amy Keating
Department of Biology, MIT
Coiled-coil dimers, in which two alpha helices intertwine to form a supercoiled bundle, are widely used to mediate interactions both in biology and materials science. Although coiled-coil reagents for inducing homo-oligomerization or hetero-oligomerization of single complexes are commonly employed, the modern coiled-coil toolkit provides limited access to more complex interaction patterns. We have expanded the possible uses of coiled coils in molecular engineering by measuring the complete pair-wise interactions of 48 synthetic coiled coils and 7 human bZIP coiled coils using protein microarrays. Focusing on those peptides that do not strongly self-associate, we have identified a 26-member protein set that includes 27 interacting peptide pairs. The interaction connectivity of these 27 pairs can be used to assemble networks of 3 to 6 proteins with a variety of interactions. Of special interest are peptide pairs that participate in mutually orthogonal interactions. These pairs provide the ability to dimerize separate molecular systems with minimal crosstalk. The interaction geometry of two of these pairs has been confirmed with both solution and crystallographic studies, and we are currently validating the in vivo behavior of the peptides in E. coli and S. cerevisiae. The variety of network motifs discovered in our screen provide new capabilities for synthetic biology and other applications. These protein reagents will be characterized in more detail and made available to the scientific community through open-source biological repositories.
International Conference on Systems Biology of Human Disease 2010 details announced
Published January 27, 2010
The International Conference on Systems Biology of Human Disease has undergone a major change in support and scope beginning in 2010. The meeting has expanded from two to three days (June 16-18, 2010) and is now supported not only by the MIT/HMS-based Center for Cell Decision Processes, but also by the Center for Cancer Systems Biology (CCSB) at Dana Farber Cancer Institute and by the iBIOS division of the German Cancer Research Center (DKFZ). In the future the conference will alternate between Boston, MA and Heidelberg, Germany (starting with Boston in 2010 and 2011 and Heidelberg in 2012). With these changes we hope to make the meeting the premier setting for discussing mammalian systems biology, particularly as it applies to human disease and therapy.
Cells, Circuits, and Computation 2010 announced - Jan. 15, 2010
Published November 17, 2009
A day-long conference on biophysics research in the Boston area. There will be two sessions with faculty speakers and one session with graduate student speakers selected from submitted abstracts. The conference concludes with a poster session. The keynote speaker is David Walt of Tufts University.
Update — January 9, 2010
Online registration is now closed. On-site registration will be offered on January 15 at the late registration rates as listed below.
Boston Area Systems and Synthetic Biology (BASS) Meeting - Dec. 9, 2009
Published November 12, 2009
This December will see the first regular gathering of the Boston Area Systems and Synthetic (BASS) Biology community. Our intention is that the BASS meeting will bring together the community and foster collaborations. The new BASS website is located at bassbiology.org.
Our model is that of the Boston Area Worm Meetings (BAWM) and Boston Area Yeast Meetings, which have done this very successfully for their respective communities. Practically, we envision meeting about every 6-8 weeks after 5pm at the Broad Institute for 3 talks from the general areas of quantitative modeling, network biology, computational biology and synthetic biology from young PIs, post-docs, and advanced graduate students.
For the first BASS meeting on December 9th 2009 in the Monadnock room at the Broad Institute, we have assembled a unique and distinguished panel of senior speakers: Aviv Regev, László Barabási and Peter Sorger. Food will be served.
We are looking forward to seeing you in December.
Pascal Braun (CCSB), Aviv Regev (Broad) & Marc Vidal (CCSB)
Supported by:
- Laszlo Barabasi (Northeastern University)
- James Collins (BU)
- Doug Lauffenburger (MIT)
- Peter Sorger (HMS)
- Bodo Stern (FAS)
Systems Biology of Human Disease conference - June 18-19, 2009
Published March 25, 2009
The Systems Biology of Human Disease conference was held on June 18–19, 2009. The conference included over 200 participants, 53 poster presenters, and 17 talks. SBHD 2010 is scheduled for June 16-18 at Harvard Medical School. Details of the 2010 conference and registration will be available via this site - check back in January 2010 for details.
CCC2009 poster prize winners announced
Published January 27, 2009
Over 30 posters were presented at Cells, Circuits, and Computation on January 23, 2009. CSB2 is happy to announce that Luke Thompson (MIT Biology) and Yoram Burak (Harvard Center for Brain Science) won the two poster prizes. The abstracts of their poster presentations follow:
Viruses hijacking cyanobacterial carbon metabolism
Luke R. Thompson1, JoAnne Stubbe1,2, and Sallie W. Chisholm1,3
Departments of 1: Biology, 2: Chemistry, and 3: Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge MA
Cyanophage infecting the marine cyanobacteria Prochlorococcus and Synechococcus carry several genes involved in the pentose phosphate pathway (PPP), a nighttime alternative to the Calvin cycle that generates NADPH and ribose. Oxidizing conditions in cyanobacteria at night, when photosystem I cannot generate NADPH, favor flux through the PPP, including the key enzyme transaldolase. Many cyanophage carry a transaldolase gene (talC) that differs markedly in structure from the host transaldolase (talA), suggesting that its acquisition and maintenance by cyanophage stems from functional differences with the host transaldolase. We have shown that the host enzyme is subject to oxidation in aerobic conditions, requiring reductant for full activity, whereas the phage transaldolase has no such effect. Site-directed mutagenesis of host transaldolase cysteines suggests that a mechanism independent of disulfide bond formation is responsible for this redox effect. We have recently found that another PPP-related gene, for the photosynthetic regulatory protein CP12, is also carried by many cyanophage. In cyanobacteria and other phototrophs, CP12 binds and deactivates two Calvin cycle enzymes under nighttime oxidizing conditions, promoting flux through the PPP. It therefore seems that cyanophage promote flux through the PPP by encoding not only enzymes but also a regulatory protein that inhibits the competing Calvin cycle. Phage infection of some cyanobacteria is known to lead to oxidizing conditions. Oxidative inactivation of host transaldolase and activation of phage CP12 may therefore be physiologically important, allowing cyanophage to produce NADPH and ribose for nucleotide biosynthesis and genome replication. Abundance patterns in phage genomes of talC, cp12, and two phage-encoded PPP dehydrogenases (zwf and gnd) are mirrored in environmental sequence databases, suggesting that the metabolic hijacking of cyanobacteria by cyanophage may be a globally important phenomenon.
Fly Magnetism: Planar Cell Polarity in Drosophila Development
Yoram Burak1,2 and Boris Shraiman2
1: Center for Brain Science, Harvard University, Cambridge, MA
2: Kavli Institute for Theoretical Physics, UCSB, Santa Barbara, CA
Cells in the wing blade of Drosophila Melanogaster exhibit an in-plane polarization causing distal orientation of hairs. Establishment of the Planar Cell Polarity (PCP) involves intercellular interactions as well as a global orienting signal. Many of the genetic and molecular components underlying this process have been experimentally identified and a recently advanced system-level model by Amonlirdviman et al (2005) has demonstrated that many of the observed mutant phenotypes can be understood in terms of intercellular interactions involving asymmetric localization of membrane bound proteins. Among key open questions in understanding the emergence of ordered polarization is the effect of stochasticity and the role of the global orienting signal. These issues relate closely to our understanding of ferromagnetism in physical systems. Here we pursue this analogy to help understand how PCP order and its response to perturbations depend on the parameters of a semi-phenomenological model of the underlying molecular processes. We define a “phase diagram” of the model which provides a global view of the dependence of the phenotype on the parameters. We show that the dynamics of PCP has two regimes: rapid growth in the amplitude of local polarization followed by a slower process of alignment which progresses from small to large scales. We discuss the response of the tissue to various types of orienting signals and show that global PCP order can be achieved with a weak orienting signal provided that it acts during the early phase of the process. Finally we define and discuss some of the experimental predictions of the model.
Cells, Circuits, and Computation 2009 full schedule available
Published January 21, 2009
The full schedule for CCC2009 (Jan 23, 2008) is now available on the event page.
Cells, Circuits, and Computation 2009: early registration now open
Published October 7, 2008
Register now for CCC2009 ($50 general, $30 students). Late registration (after December 15, 2008) is possible at an additional charge. View the full event details for CCC2009 here.
CSB2 prizes awarded to Aneil Mallavarapu and Gavin MacBeath
Published August 4, 2008
CSB2 has named Harvard researchers Aneil Mallavarapu and Gavin MacBeath as the winners of its 2008 Innovation awards.
The Merrimack-CSB2 Prize was awarded to Aneil Mallavarapu, a senior research scientist in the Harvard Medical School Virtual Cell Program, for his work on little b, an open-source LISP-based language for building modular, shareable, and scalable models of biological systems. The Merrimack-CSB2 Prize is awarded annually to a young scientist for exceptional contributions to the development and application of innovative modeling and computational methods as judged by technical quality, broad utility and fundamental theoretical insight.
“Aneil Mallavarapu is one of those rare scientific talents who combines a deep understanding of molecular and cellular biology with a mastery of computational technology,” said Jeremy Gunawardena, HMS senior lecturer on systems biology and director of the Virtual Cell Program. “His development of the little b computational infrastructure marks a key step on the road to postgenomic in silico biology and has profoundly improved our ability to construct in silico models of biological systems.”
The Pfizer-CSB2 Prize was awarded to Gavin MacBeath, associate professor of chemistry and chemical biology at Harvard University, for the development of new protein microarray methods applicable to the study of signal transduction, disease, and targeted therapy in humans.