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Principal Investigator:

Leonid Mirny
Junior Fellow, Harvard Society of Fellows
Ph.D., Harvard Biophysics
M.Sc. Chemistry, Weizmann Institute of Science
Biosketch @ MIT Computational and Systems Biology
Biosketch @ MIT Physics


Graduate Students:

Geoff Fudenberg
Harvard Biophysics, Ph.D. Student

3D Genome Organization: Physical models, statistical methods, and comparative genomics


Maxim Imakaev
MIT Physics, Ph.D. Student


Jason Leith
Harvard Biophysics, Ph.D. Student

Several classes of proteins, including transcription factors, DNA-repair enzymes, and restriction enzymes, bind highly specifically to one or a few particular sites on a genome of millions to billions of base pairs. These proteins often are able to locate, using only thermal energy, and bind to their specific sites orders of magnitude faster than simple 3-D diffusion would allow. How they find their sites and recognize them so quickly, while avoiding "mislocalization", is not fully understood. Recent single-molecule experiments have verified predictions that these proteins would bind non-specifically to DNA and undergo 1-D diffusion in order to speed up the search process. Our lab has proposed that these sliding proteins undergo a conformational transition between a fast-sliding state and a stable-binding state, so that they can locate their cognate sites quickly and still bind securely. Very recent structural studies that have shown that the conformation of transcription factors and restriction enzymes indeed differs depending on whether the protein is bound to its cognate site or to a non-specific sequence. My work involves simulating the search, re-folding, and binding processes to better understand the physical parameters that govern the efficiency and stability of target binding. Additionally, I collaborate with Antoine van Oijen's group at Harvard Medical School in performing single-molecule microscopy experiments that examine the dynamics of p53's sliding on DNA.


Chris McFarland
Harvard Biophysics, Ph.D. Student

Precancerous cells acquire thousands of mutations as they evolve into a malignant population, yet only a handful of these occur in genes believed to be directly related to the neoplastic phenotype. Based on evidence from the Cancer Genome Project, we have found that many of these previously ignored mutations, termed passenger mutations, have subtle effects on the cancer population that in many cases harm cancerous cells. I am interested in understanding these mutations further. Using theory from evolutionary genetics, we are trying to explain how passenger mutations arise in the population, despite their deleterious phenotypes, and how they effect growth. We have found many genetic and biophysical features of these passenger mutations within the genes and proteins that harbor them that allow us to phenotype, and potentially exacerbate, their effects on cancer. This project is part of a collaborative effort where I am working with the Sunyaev Lab to integrate our understanding of mutational patterns in cancer with their prior methods for phenotyping germ-line mutations using comparative genomics. We are then testing our models of passenger mutations in two ways: against recent whole-genome DNA sequence of cancers with Dr. Gaddy Getz at The Broad Institute and by studying the effects of these mutations in cell culture in conjunction with the Sherman Lab. Most recently, we have extended our research on passenger mutations towards cancerous cells which colonize into metastases; ''In silico'' results suggest that these populations are particularly susceptible to the effects of passenger mutations and we are exploring this possibility in a mouse model with researchers at .


Michael Schnall-Levin
MIT Mathematics, Ph.D. Student

Transcriptional Regulation: Factors\A0Beyond Binding Motif Matches


Rotation Students:

Jaie Woodard
Harvard Biophysics, Ph.D. Student


Ivan Adzhubey
Moscow State University, Ph.D. in Biology
Bioinformatics infrastructure development and maintenance
Vincent B\E9rub\E9, Ph.D. Student
MIT Physics, Ph.D. Student
Stochastic models of ion channels
Juhi Chandalia, Masters Student
MIT, B.S., M.S.
Structure and evolution of regulatory networks
Carlos G\F3mez-Uribe, Ph.D. Student
Stochastic models of signaling networks
Grigory Kolesov, Postdoctoral Fellow
University of Munich, Ph.D. in Biology
Evolution and prediction of specificity-determining residues
Hao Yuan Kueh, Rotation Student
Harvard Biophysics
Princeton University, B.S.
Information transmission in enzymatic switch
Joe Levine, Masters Student
MIT, B.S., M.S.
Dynamics of signaling cascades
Lewyn Li, Postdoctoral Fellow
Columbia University
Harvard University, Ph.D. in Chemistry
Specificity determining residues in protein kinases
Shankar Mukherji, Undergraduate Student
Dynamics of signaling cascades
Ilya Rudkevich, Undergraduate Student
Brandeis University, B.S.
Prediction of natively unstructured proteins
Alex Shpunt, Ph.D. Student
MIT, Ph.D. in Physics
Biophysics of molecular self-assembly
Michael Slutsky, Ph.D. Student
MIT, Ph.D. in Physics
Biophysics of protein-DNA interactions
Victor Spirin, Postdoctoral Fellow
Boston University, Ph.D. in Physics
Structure and regulation of biological networks
Anahita Tafvizi, Ph.D. Student
Harvard University, Ph.D. in Physics
Transcription factor-DNA interactions
Zeba Wunderlich, Ph.D. Student
Harvard University, Ph.D. in Biophysics
Modeling of the transcription factor search process
Energetics of protein-protein interactions

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