People

Daniel Weinreich, PhD 
Principal Investigator
Associate Professor of Biology
Ecology & Evolutionary Biology and Center for Computational Molecular Biology 

Office: 300 Walter Hall (401)/863-3937
Lab: 528 BioMed Center (401)/863-2749

Office Hours: By appointment and Wednesdays 1 - 3 during the fall term

Daniel_Weinreich at brown dot edu

Dr. Weinreich's Curriculum Vitae.pdf

 

POSTDOCTORAL FELLOWS

Christopher Scott Wylie, PhD 
BA Rice University 2000
PhD University of California San Diego 2009

Christopher_Scott_Wylie at brown dot edu

On the broadest level, the goal of my research is to understand how (and indeed if), the blind process of evolution can sort through, and thus select for, subtle variations in fitness.  This challenge is especially acute when "fitness" is not conceptually clear-cut, e.g. in the following examples of ongoing projects:
  • Mutation rate evolution:  Variants that modify the fidelity of genomic duplication (i.e. "mutators") alter the fitness of future generations but not the current one.  We are using both computer simulations and laboratory evolution of E. coli to study the effect of population size on mutation rate evolution.  
  • Evolution of mutational robustness:  Variants that modify the severity of new deleterious mutations are said to confer "mutational robustness."  Contrary to established theory, we hypothesize that evolution cannot select for mutational robustness, i.e. that lack of robustness results from an inherent "blind spot" of evolution.  We are testing this hypothesis with a combination of population-genetics theory and experimental evolution of an antibiotic resistance enzyme (TEM-1 beta lactamase).  
  • Biophysical underpinnings of mutational effects:  The issue of whether new mutations have mild or drastic fitness effects ultimately depends on chemical and physical constraints.  An increasingly popular hypothesis is that most new mutations compromise a protein's function via their impact on protein thermodynamic stability.  We are currently utilizing biochemical, biophysical, and genetic approaches to test the "stability hypothesis," using beta lactamase as a model system.  

Eugene Raynes, PhD 
BA New York University 2006
PhD University of Pennsylvania 2012

Yevgeniy_Raynes at brown dot edu

I use experimental evolution and computer simulations to study evolution of the genomic mutation rate. During my PhD I examined the evolutionary dynamics of mutator alleles in experimental microbial populations, focusing on indirect selection experienced by mutators due to their associations with beneficial mutations. Currently, I am using computer simulations to investigate the evolutionary dynamics of chromosomal instability during cancer progression.

Chintan ModiChintan ModiChintan Modi, PhD 
BA Penn State University 2000
PhD University of Austin at Texas 2014

Chintan_Modi at brown dot edu

I am interested in understanding the evolution of structure-function relationship of proteins. Specifically, I am working to understand how novel biochemical function evolves.  Currently I am studying the emergence of antibiotic resistance by asking how a novel ß-lactamase function evolved from penicillin-binding proteins (PBPs).  Part of this study also plans to understand the evolution of generalist vs. specialist ß-lactamases. To answer these questions I am plan to use directed evolution and ancestral reconstruction through statistical phylogenetic methods. I also remain interested in understanding the evolution of homo-oligomerization. Prior to join the Weinreich lab, I studied the evolutionary biochemistry of the GFP-family of proteins using resurrected ancestral fluorescent proteins. My research help elucidate the initial historical mutations needed to enable the evolution of novel biochemical step in emergence of red fluorescence in Kaede FPs and showed evolution of diverse homo oligomers from an ancestral monomer the hydrozoan FPs.  



 

GRADUATE STUDENTS

Christopher Graves
Graduate Student
BS University of Vermont 2009

 

NSF Graduate Research Fellowship 2013 - 2016
NSF Doctoral Dissertation Improvement Grant 2015 - 2016

Christopher_Graves at brown dot edu

Natural selection is inherently short-sighted, favoring traits based on their immediate effects on survival and reproduction. However, natural environments are constantly changing, and thus the fitness effects of many traits are variable through time. My research examines the consequences of this temporal variation in fitness and the role it plays in adaptation. Current projects include developing mathematical models and simulations to explore the consequences of variable selective pressures in the evolution of infectious diseases and experimental work to test predictions of evolutionary theory by tracking the evolutionary dynamics of yeast populations as they evolve in a variable environment. 


Yinghong Lan

Graduate Student
BS University of Science and Technology of China 2012

Yinghong_Lan at brown dot edu

My general interest includes fundamental theoretical questions in the fields of population genetics and evolutionary genetics, and testing these ideas using simulations and microbial experiments. Recently I have been working on understanding mutational robustness, i.e., the ability to sustain fitness against deleterious mutations. Combining analytical with simulation approaches, our research show that in contrast to the conventional wisdom, flatter regions of the fitness landscape cannot confer long-term resilience against mutations. We propose instead that fitness “domes”, i.e., fitness peaks with negative epistasis, is where selection would drive populations constantly facing the challenge of high mutation rates. I’m currently testing this hypothesis using both Wright-Fisher simulations and directed evolution of TEM-1 ß-lactamase in E. coli.

 

Current Undergraduates

Selena Buzinky '15
Natasha Nguyen '15
Caleb Weinreb '15
Dylan Spangle '16
Isaiah Bryant '17
Chibuikem Nwizu '17
Sovijja Pou '17
Julia Gross '18

Alumni