Theory Lunch this week

Dynamical bases of cellular heterogeneity

Jordi Garcia-Ojalvo
Department of Physics
Technical University of Catalonia, Spain

29 June 2012, 12-1.30 pm, WAB 563

Abstract
Cellular heterogeneity is frequently associated with the stochasticity of biochemical reactions within the cell. However, there are other mechanisms through which heterogeneous behavior can arise in cell populations. In these scenarios noise plays only a secondary role, being filtered by gene and protein circuits leading to a dynamical behavior that is unsynchronized across the population. In this talk I will discuss examples of these types of mechanisms in the particular case of embryonic stem cell pluripotency, which is known to be both strongly dynamical and heterogeneous. I will explore what we can learn from the observed heterogeneity in the levels of pluripotency factors, and from measurements of the correlated heterogeneity in pairs of such factors under different signaling scenarios. Within that context, I will present a theoretical model of pluripotency that reproduces these observations reasonably well, potentially leading us to a better understanding of the nature of pluripotency.

TL schedule here.

Book launch party!

As I have mentioned before, Angela DePace has written an excellent book on visualizing your data, with Felice Frankel.

The Post-doc Office at HMS is now sponsoring a Book Launch and Reception as part of their Communicating your Science series, and they’re even going to have a raffle to win a copy of the book.

When: Monday, June 25 | 3:00-4:30pm
Where: Waterhouse Room, Gordon Hall, HMS

Join us for an author talk and book launch party as Angela and Felice introduce their recently released book, Visual Strategies: A Practical Guide to Graphics for Scientists and Engineers. Visual communicator Felice Frankel and systems biologist Angela DePace demonstrate how small changes can vastly improve the success of a graphic image. They dissect individual graphics, show why some work while others don’t, and suggest specific improvements.

RSVP (Required) here.

Theory lunch this week

Origin-dependent inverted repeat amplification in yeast

Maitreya Dunham
Department of Genome Sciences
University of Washington

Friday, 22 June 2012, 12-1.30 pm

Abstract
I will talk about a proposed new mechanism of gene amplification in yeast. In continuous cultures propagated under low concentrations of sulfate, amplification of the transporter gene, SUL1, provides an enormous fitness gain. However, unlike the other CNVs that we have found during experimental evolution, SUL1 is not adjacent to any obvious repeat sequences that could explain its amplification. We sequenced a collection of independently evolved strains and discovered a novel inverted tandem repeat, flanked by short hairpins. The structure can’t easily be explained by other known mechanisms of DNA rearrangement. We think that this event is created by a previously unrecognized error in replication, and that it may contribute to unexplained inverted repeats in other systems, including cancer.

TL schedule here.

Theory Lunch this week

Investigating functional roles of circadian rhythms in Neurospora crassa

Christian Hong
Department of Molecular and Cellular Physiology
University of Cincinnati College of Medicine

15 June 2012, WAB536, 12-1.30

Abstract
Fundamental cellular processes that maintain most organisms’ health and survival include cell cycle, DNA damage response, and circadian rhythms. Cell cycle is equipped with multiple checkpoints for controlled growth, DNA replication, and divisions. DNA damage response (DDR) mechanisms control cell fate by either repairing single or double strand breaks, or triggering apoptosis for programmed cell death when the damage is fatal. Last, but not least, is circadian rhythm that keeps track of time of a day, and plays a central role in most organisms for setting the sleep/wake cycle, feeding rhythms, and other daily activities. These distinct molecular mechanisms communicate with each other and create a complex bio-molecular network to optimize conditions for cells to grow and adapt to the surrounding environment. We explore functional roles of circadian rhythms in other cellular processes such as cell cycle employing mathematical modeling and experimental validations using the model organism Neurospora crassa.

Current TL schedule here.

Theory Lunch this week

Modeling cell decisions: two case studies

James Faeder
Department of Computational Biology
University of Pittsburgh School of Medicine

8 June 2012, 12-1.30 pm, WAB 563

Abstract
In this talk I will discuss ongoing collaborative efforts to develop quantitative models of two cell signaling processes that have both basic and applied significance: bacterial spore germination and T cell differentiation.

Despite consuming undetectable amounts of energy, bacterial spores have the ability to sense small quantities of the nutrients in their environment and to re-enter a growing state within minutes. At the same time, a population of spores exhibits a high degree of heterogeneity in the response time. Here, I will present a quantitative model of bacterial spore germination that reproduces experimental data for heterogeneity in germination times with a single nutrient and that we have used to infer the mechanism for signal combination under conditions where two nutrients are present.

Peripheral naive T-cells can differentiate into several types of effector cells and the relative numbers produced of each cell type are critical for many immune-related pathologies. To study this system, we have constructed a logic circuit model in which each molecule type is treated as a discrete variable and variable values are updated according to logic rules. The model reproduces several important experimental observations and its construction helps to clarify the logical relationships among molecular inputs at several key control points in the process. We also find that the interplay of stimulation strength and duration plays a critical role in cell fate decision. In particular, there appears to be a critical period of signaling during which removal of antigen stimulation can produce a wide range of phenotypes. Branching between these dominant phenotypes, T helper and T reg, is affected by the timing of activation or inhibition of several key biochemical pathways controlling the differentiation process.

TL schedule here.

Theory lunch this week

Understanding collective behavior

Radhika Nagpal
School of Engineering and Applied Sciences
Harvard University

Friday, June 1, 12-1.30, WAB 563

Abstract
Social insects and cells show many striking similarities in the way they solve problems collectively — task differentiation, symmetry-breaking, synchronization, self-assembly. In the first half of the talk, my goal is to explore (interactively) the following question: is it possible to identify a catalog of “problems & solutions” that have evolved for collective decision-making? In the second half of the talk I will describe and show some demonstrations of the kilobot robot swarm system that we have developed to study collective behaviors.

current theory lunch schedule here

Theory Lunch this week

The dynamics of exponential growth

4 May 2012, 12-1.30pm, Warren Alpert 563, HMS

Alexander van Oudenaarden
Systems Biology Lab
Departments of Physics and Biology, MIT
AND
Hubrecht Institute for Developmental Biology and Stem Cell Research
Utrecht, Holland

Abstract
Since the pioneering work of Jacques Monod in 1941, the diauxic growth of bacteria or yeast, and especially the phase of exponential growth, has been a central experimental paradigm, which is used on a daily basis. Despite the historic familiarity of the diauxic growth, many aspects of cell growth and physiology during the diauxic growth have not been quantified. We quantified metabolic fluxes, oxygen consumption and carbon dioxide production during a full time-course of the diauxic growth of budding yeast and made two surprising discoveries. First, we find that during the exponential growth phase yeast cells can substantially change their metabolic state reflected in major changes in glucose uptake, respiration and fermentation even while the growth rate remained constant. These metabolic changes were reflected in major changes in gene expression, underscoring the observations that a constant growth rate does not necessarily indicate a steady-state growth and that cells can maintain a constant growth rate using very different metabolic strategies. Our second surprising discovery is the sign of the flux changes: as glucose was gradually depleted from the growth medium, a larger fraction of the glucose taken up by the cells was fermented to ethanol, and consistently the rate of oxygen consumption per cell decreased. These fluxes are in stark contrast with the current steady-state model assuming that the rate of fermentation is proportional to the glucose concentration and the rate of glucose uptake. Our results, taken together, demonstrate that quantification of the absolute rates of respiration and fermentation is essential to understanding cell growth and will help to characterize the trade-offs inherent to each metabolic strategy.

TL schedule here.

Network Science in Biology and Medicine Symposium

Harvard Catalyst is sponsoring a symposium on Network Science in Biology and Medicine on Thursday, June 7, 2012, in the Amphitheater of the Joseph B. Martin Conference Center at HMS.

Symposium: 4:00pm – 6:30pm
Reception: 6:30pm – 7:00pm

The Network Science in Biology and Medicine Symposium will offer an introduction to a rapidly emerging field that combines systems biology and network science by focusing on the identification and investigation of networks of interacting molecular and cellular components. When integrated into biomedical research, network medicine has the potential to transform investigations of disease etiology, diagnosis, and treatment.

Program:

Co-chairs: Joseph Loscalzo, MD, PhD and Marc Kirschner, PhD.

Complex Networks in Biology – Albert-Laszio Barabasi, PhD, BWH

Network Medicine: A New Paradigm for Defining Human Disease and Therapy – Joseph Loscalzo, MD, PhD, BWH

Microbial Evolution within a Human Host – Roy Kishony, PhD, HMS

Systems Pharmacology – Peter Sorger, PhD, HMS

Please register by May 21, 2012.

And… Synthetic Biology in Space!

National Aeronautics and Space Administration

THE NASA AMES RESEARCH CENTER IS DEFINING THE FIELD OF SPACE SYNTHETIC BIOLOGY

Applications are invited for an experienced research scientist to join NASA Ames in defining the field of Space Synthetic Biology.  Building on decades of cutting edge scientific achievements, NASA Ames Research Center is creating a new, interdisciplinary, research effort to use synthetic biology as an enabling technology to explore our solar system.

NASA recently established a new Space Synthetic Biology Project at NASA Ames Research Center that has been funded to perform breakthrough research to harness biology to create reliable, robust, engineered systems.  These systems will support NASA’s exploration and science missions, improve life on Earth, and help shape NASA’s future. With the promise of engineered biology on Earth within reach, the Space Synthetic Biology Project aims to develop advanced technologies for Synthetic Biology applications in space.

NASA Ames Research Center is seeking to hire an experienced research scientist to develop a new, high profile interdisciplinary Space Synthetic Biology research effort and play a key role in defining this exciting new field for NASA.  We are seeking researchers who will create advances in both enabling biological technologies and foundational tools tomake biological systems easier to engineer for applications in biological life support and/or in-situ resource utilization for the production of food, biomaterials and resource extraction.  You will have the opportunity to collaborate with our current partners including University of California Santa Cruz, Stanford, and the Venter Institute. This is a full time, permanent position, which includes a highly competitive start-up package.

In addition, the successful candidate will be responsible for further developing NASA’s partnership with its University Affiliated Research Center managed by the University of California, Santa Cruz (UCSC).  Within the appropriate responsibilities of this NASA position, an official assignment to interact with UCSC faculty and students as an Adjunct Professor will be pursued for the successful candidate.  This official assignment may allow the candidate to participate in teaching courses and further develop collaborations with UCSC scientists in support of NASA’s mission.

At NASA, your research could change our world and enable exploration of new ones.

US Citizenship is required.

Interested applicants should apply directly to USAJobs to vacancy AR12B0018 at:
http://www.usajobs.gov/GetJob/ViewDetails/311548900

NASA Ames Research Center does not discriminate in employment on the basis of race,color, religion, sex, national origin, political affiliation, sexual orientation, gender identity, marital status, disability and genetic information, age, membership in an employee organization, or other non-merit factor.

Theory Lunch this week

DNA as a universal substrate for chemical kinetics

27 Apr 2012, 12:00-1:30 pm, Warren Alpert 563, HMS

Erik Winfree
Computer Science, Computation
and Neural Systems & Bioengineering
Caltech

Abstract
Formal chemical reaction networks (CRNs) provide an elegant standard language for describing and analyzing well-mixed systems of interacting particles. Taking a complementary approach, I will discuss recent work showing how CRNs can be used prescriptively, rather than descriptively, as a programming language for creating complex nucleic acid systems.

References

D Soloveichik, G Seelig, E Winfree (2010) DNA as a universal substrate for chemical kinetics, PNAS 107:5393-8

Current TL schedule here.