Microbial Evolution Meetings at Harvard

September 2012: for up to date info see the new website

Since November 2010, Sergey Kryazhimskiy and I organize seminars by and for people who work on evolution in microbial systems, using theory, experimental evolution, patient data etc. We aim to bring together people from different departments/institutes of Harvard (OEB, Genetics, Systems, School of Public Health etc) who work on evolution of microbes. The seminars usually take place in the NorthWest building on Oxford Street in Cambridge. If you want to be added to our mailing list, or if you would like to speak, send an email to pennings at fas.harvard.edu

The schedule for spring 2012 is finalized! See below

Schedule Spring 2012 

Meetings are at 5PM on Thursdays in Northwest Building Room 353

January 26th 2011 Sergey Kryazhimskiy (Desai Lab): Champions and losers in a race to the top: epistasis and adaptation in yeast. 

ABSTRACT: We know that populations adapt when they encounter new environments, but our ability to predict the course and rate of adaptation are currently very limited. One complication is that we do not know how one mutation might influence the fitness effects of other mutations. In other words, we do not know the structure of epistasis among beneficial mutations. I will describe some experiments that are aimed at probing the statistical structure of epistasis among beneficial mutations and the implications of our findings for the predictability of adaptation. 

February 9 2012 Adrian W.R. Serohijos (Shakhnovich lab): Imprints of protein biophysics on the molecular clock

ABSTRACT: Evolution is a dynamic process acting at multiple length and time scales—single mutations affect the molecular properties of DNA/RNA/proteins, consequently increasing or decreasing organismal fitness. The mutation’s fate is likewise dictated by population size since species survive or become extinct in the wild as a population. I will describe our efforts to create a systematic framework that bridges these scales. I will also present some results that address outstanding questions on the nature of the molecular clock.

February 23 2012 Gregg Wildenberg (Murray lab): Evolution of a Circadian Clock in Yeast

ABSTRACT: I seek to understand the molecular basis of evolutionary novelty.  I have experimentally evolved a circadian clock in Saccharomyces cerevisiaeto ask how an organism evolves a new function and will identify the molecular and cellular changes that gave rise to this novel behavior.  

March 1 2012 Alison Hill (Nowak lab): Predicting and preventing drug resistant HIV at multiple levels of selection

ABSTRACT: The evolution of drug resistance in HIV is an example of selection occurring at multiple spatial and temporal scales. First, I will discuss techniques we have developed to study the emergence of drug resistance within a host, including adapting the mutant selection window to virology and attempts to realistically simulate clinical trials. I will present results on how pharmacodynamics and pharmacokinetics of antiretroviral drugs affect the generation and selection of resistance mutations, and how this is influenced by viral latency, drug-protected compartments in the body, and different modes of cell-to-cell transmission. Secondly, I will discuss the population wide evolution of HIV, including the potential for a drug-resistant epidemic and models for how the spread of new disease variants in influenced by population structure. 

March 22 2012 Liedewij Laan (Murray lab): How evolvable are polarization mechanisms?

ABSTRACT: Why do cells simultaneously use different polarization mechanisms and why do even closely related species seem to use a different variety of them? We removed genes essential to a specific polarization mechanism in yeast and subsequently evolved these “nearly dead” cells to significantly higher fitness. I will present our first attempts to study how these cells fixed the “deleted” mechanism.

April 5th 2012: John Coffin (Tufts University): Host-retroviral coevolution 

John Coffin is a professor at Tufts and the director of the HIV Drug Resistance Program of the National Cancer Institute, going back and forth between Boston and Bethesda almost every week. He is also a member of the National Academy of Sciences. 

John is well knwon for his work on HIV. His 1995 Science paper is hugely influential (with >1600 citations) and many of his newer papers on HIV are important too. However, he has also done a lot of work on other retroviruses including endogenous retroviruses. Such viruses are present in high numbers in our genome and can be used to study our evolutionary history as well as the history of the viruses. This is what he will talk about. 

April 19th 2012: Wolfram Moebius (Nelson lab): Range expansions into heterogeneous environments

Wolfram says: "I'm interested in how a species spreads into new territory which is not homogeneous, but heterogeneous (think as mountains or lakes as obstacles in the plains). To investigate this question, I try to use a combined theoretical and experimental approach using a model system of bacteriophage T7 spreading on a (heterogeneous) lawn of E. coli."

May 10th 2012 Genya Frenkel (Desai lab): Tracking dynamics of adaptation reveals the distribution of fitness effects and evolution of ecology in asexual budding yeast

Tracking the frequencies of neutral markers in a population is a classic way to observe the dynamics of adaptation, in particular the appearance of beneficial mutations and their subsequent trajectories toward fixation or loss. I will present the results of a relatively large-scale study of this kind. Into ~1000 identical populations of budding-yeast, I seeded mutants with known initial fitness advantages and frequencies. I observed their trajectories to be at-first deterministic, as expected, and subsequently highly variable. The goal is to infer from the statistics of these outcomes (e.g. fixation probabilities) information about the rate and distribution of fitness effects of beneficial mutations. In some cases, the populations evolved into two types that co-exist at a stable equilibrium ratio, which was found to be dependent on the spatial structure of the population at the bottom of microtiter wells.

May 17th 2012 Ariel Weinberger (Gilmore lab) Adaptive Immunity: Why some microbes have it and others don't.

Bacteria and archaea have elegant adaptive immune systems that target and destroy specific viral and plasmid DNA sequences. Termed CRISPR, these adaptive immune systems are found in over 90% of archaea but only 50% of bacteria. I'll combine genomics and modeling to try to explain the relative lack of CRISPR in bacteria, capturing thresholds in the viral mutation rate above which CRISPR cannot evolve.

May 31st 2012 Kirill Korolev (MIT) Deleterious mutations in cancer

Abstract: Cancer is an outcome of somatic evolution. To outcompete their benign sisters, cancer cells need to acquire many heritable changes (driver mutations) that enable proliferation. In addition to the rare beneficial drivers, cancer cells must also acquire neutral or slightly deleterious passenger mutations. Indeed, the number of possible passengers exceeds the number of possible drivers by orders of magnitude. Upon including passengers in our model, we found that cancer is no longer a straightforward progression to malignancy. In particular, there is a critical population size such that smaller populations accumulate passengers and decline, while larger populations accumulate drivers and grow. The transition to cancer for small initial populations is, therefore, stochastic in nature and is similar to diffusion over an energy barrier in chemical kinetics. We also found that there is an optimal mutation rate for cancer development, and passengers with intermediate fitness costs are most detrimental to cancer. Our theory can explain some paradoxes in cancer research and is consistent with recent sequencing data. Finally, we show that cancer's position in the parameter space can be crucial for selecting the most successful treatment. 

Past seminars (2010-2011) 

December 12 2011 Tim Van Opijnen (Tufts University): The virulence landscape of a bacterial pathogen. Tim's Website.

November 28 2011 Nigel Delaney (Marx lab): Insights into evolution from the fastest evolving bacteria on earth.

November 14 2011 Will Harcombe (Marx lab): Evolution of complex networks: Testing the predictions of flux balance analysis.

October 31 2011 Melanie Müller (Nelson lab): Range expansion of mutualists.

October 3rd 2011 Hsiao-Han Chang (Hartl lab): Population genetic inferences of Plasmodium falciparum on fully sequenced genomes from Senegal. 

September 19th 2011 John Koschwanez (Murray lab): Sticking together makes life sweeter. See recent story in Harvard Gazette

June 13th 2011 Rolf Ypma (The Netherlands Institute of Health): "A statistical framework for reconstructing transmission trees: avian influenza as a case study" 

June 1st 2011 Daniel Rosenbloom (Harvard, FAS, OEB) "The Good, the Bad, and the Ugly: Predicting HIV treatment success, failure, and drug resistance using a model of virus dynamics"

March 21st Tami Lieberman (Harvard, HMS, Systems): "Genomic evolution of a bacterial pathogen within human hosts"

February 22nd 2011 Gabriel Perron (Harvard, FAS, Systems): "The evolution of antibiotic resistance: insights from field and experimental studies"

February 7th 2011 Scott Wylie (Harvard, FAS, Chemistry):  "How molecular biophysics constrains fitness landscapes"

December 13th 2010 Pleuni Pennings (Harvard, FAS, OEB): "Modeling the evolution of drug resistance in HIV"

November 30th 2010 Deepa Agashe (Harvard, FAS, OEB): "Selection against synonymous mutations"