April 21, 2016 § Leave a comment
It’s very exciting to announce that our very own Debbie Marks has won the Overton Prize from the International Society for Computational Biology (ICSB). The Overton Prize recognizes early to mid-career scientists who are emerging leaders in computational biology and bioinformatics, and is offered in memory of G. Christian Overton, a leading bioinformatics researcher and a founding member of the ISCB Board of Directors. Previous winners include many of our friends, including Uri Alon, Olga Troyanskaya and Aviv Regev. The prize committee obviously has outstanding taste!
October 25, 2012 § Leave a comment
A programmable DNA origami shuttle to study the dynamics of motor protein ensembles
26 October 2012, 12:00-1.30 pm, Warren Alpert 563 – HMS
Department of Cell Biology
Harvard Medical School
Bi-directional microtubule-based transport in eukaryotic cells drives the movement of intracellular components, allowing cells to move, divide, communicate with neighboring cells, and maintain cellular homeostasis. We built a system composed of both biological and synthetic parts to determine how the opposite-polarity molecular motors dynein and kinesin achieve bi-directional transport of cargo on microtubules. We used three-dimensional DNA origami to build a synthetic cargo structure, to which cytoplasmic dynein and kinesin-1 motors can be linked. The modularity of DNA origami allows us to control cargo size and shape and precisely encode the type, number, density, and spacing of motors. I will discuss our recent empirical studies, which investigate how motor number and type affects cargo movement in vitro.
TL schedule here.
October 18, 2012 § Leave a comment
What cell shape oscillations tell us about cortical actin-microtubule interactions and amoeboid migration
Friday, 19 Oct 2012, 12:00-1:30 pm, Warren Alpert 563, HMS
Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill
Many cellular responses to environmental stimuli involve large-scale changes in cell morphology. For example signaling molecules, such as hormones or growth factors, can induce cell differentiation, proliferation, or migration. These global changes in cell shape are highly coordinated and require dynamic regulation of the actin cytoskeleton. Therefore understanding how the actin and microtubule cytoskeleton and associated regulatory proteins function as an integrated system is a central challenge for cell biology. The morphological oscillations that occur during cell spreading are ideally suited for performing a systems-level investigation into the biochemical and biomechanical mechanisms that drive changes in cell shape. In the broader context, these oscillations constitute a mechanochemical prototype of how signaling networks regulate cytoskeletally driven mechanical behavior that in turn feeds back to modulate the signaling network. Importantly, fluorescently labeled cytoskeletal proteins and fluorescent biosensors allow dynamic structural features of the actin-based cortex and spatiotemporal activity of signaling molecules and visualized. I will discuss what we know about the dynamic structural changes in the actin cortex during oscillations, how Rho proteins regulate these oscillations, how this model may be related to amoeboid migration and emerging theoretical models for this phenotype. If time permits, I will also discuss a new paradigm for membrane domains based on pathogen receptors located on the surface of dendritic cells.
TL schedule here.
October 12, 2012 § Leave a comment
Here are the details on the inaugural Biomathematics Seminar presentation:
Alison L. Hill – Biophysics Program, Harvard University
Going viral: Modeling the dynamics of HIV treatment
Harvard School of Public Health, FXB Building, Room G13, Wednesday October 17th, 4-5 pm
Abstract: I’m a graduate student in Biophysics and HST, and work with Martin Nowak at the Program for Evolutionary Dynamics on the Cambridge campus. My research uses mathematical models to understand how diseases spread and evolve at multiple scales, with a particular focus on the dynamics of anti-HIV drugs. I will discuss our recent work focusing on two of the major shortcomings of current antiretroviral drugs used against HIV – the development of drugs resistance, particularly in patients with suboptimal adherence, and the inability of these drugs to completely eradicate the infection from the body. First, I will discuss techniques we have developed to study the emergence of drug-resistant HIV within a patient, highlighting how we integrate models with laboratory data and measures of patient behavior. I will present results on how pharmacological properties of antiretroviral drugs affect the generation and selection of resistance mutations, and our attempts to realistically simulate clinical trials. Secondly, I will discuss our models of a new drug class, which may be capable of reversing viral latency and hence permanently curing patients with HIV. We can predict the threshold efficacy required of these investigational drugs and suggest important output metrics for planned drug trials. Our preliminary results suggest that the field may be overly optimistic about the potential of current drug candidates, but that a few important yet unknown parameters prevent definitive assessment. These projects are conducted in collaboration with Bob Siliciano’s group at Johns Hopkins.
Schedule for future talks here.
October 12, 2012 § Leave a comment
Trade-offs of aerobic glycolysis
Nikolai Slavov, Oudenaarden group, MIT
Today, 12 October 2012, 12:00-1.30pm, Warren Alpert 563 – HMS
Most cells can derive energy from glucose either by oxidizing it completely to carbon dioxide and water, i.e. oxidative phosphorylation, or by fermenting the glucose to ethanol/lactate. It has been known for a century that under some conditions cells ferment glucose into ethanol/lactate even in the presence of sufficient oxygen to support oxidative phosphorylation. This process, known as aerobic glycolysis, appears surprising since oxidative phosphorylation has higher energy yield per glucose molecule than fermentation. Thus, numerous studies have suggested many elegant mechanisms that, theoretically, can rationalize aerobic glycolysis and yet some of these mechanisms are mutually incompatible. Instead of examining existing hypotheses and models, we measured metabolic fluxes, rates of respiration and fermentation in budding yeast growing across a wide range of conditions, aiming to identify experimentally trade-offs associated with aerobic glycolysis. We used these data to eliminate theoretical possibilities and constrain as much as possible the systems-level physiological responses and adaptations of cell growth to different nutrient environments and growth rates. Our flux data, combined with simple analysis based on mass-conservation, suggest inherent trade-offs in respiration and fermentation. I will discuss how some of these trade-offs can be understood in terms of first principles.
TL schedule here.
October 5, 2012 § Leave a comment
We’re recruiting! Official ad here.
The Department of Systems Biology at Harvard Medical School invites applications for a tenure-track Assistant Professor position. We seek broad and careful thinkers with strong theoretical foundations (e.g. in physics, mathematics, or computer science) who have a demonstrated commitment to tackling challenging biological or medical questions. Harvard Medical School offers a unique concentration of biomedical expertise, and the Department of Systems Biology has created a supportive and interactive environment for researchers with quantitative and theoretical skills. The successful candidate will become a member of the university-wide Ph.D. Program in Systems Biology, which has an established record of attracting extraordinary graduate students.
The deadline for applications is November 30, 2012. Candidates should have a Ph.D. in a relevant discipline or an MD.
To apply, please submit a statement of research interests (~ three pages), a curriculum vitae, and the names and e-mail addresses of at least three colleagues who have agreed to write letters of recommendation to https://academicpositions.harvard.edu/postings/4336. Once you apply, your recommenders will be prompted to submit their letters on this application portal; please make sure your recommenders submit their letters before the deadline.
Candidates should have a Ph.D. in a relevant discipline or an MD.
Applications from, or nominations of, women and minority candidates are encouraged. Harvard is an affirmative action/equal opportunity employer.