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MEMP - Thesis Defense - Atray Dixit

Friday, May 4, 2018

Broad Auditorium - Broad Institute, 415 Main St., Cambridge, MA

Bounding Genetic Nonlinearities

It is a hallmark of life to be comprised of complex hierarchical structures. Within multicellular organisms, the building blocks of these structures are cells; within cells, they are genes. The interdependence of these building blocks is difficult to measure but is integral to our understanding of biology. From tumor suppressor/oncogene mutations in cancer, X-linked recessive genetic diseases, and transcription factor cocktails used to reprogram differentiated cells into stem cells, biological processes emerge from the dynamism of thousands of interacting genes. However, it is experimentally impossible to test all possible interactions between members of any sizable set.

Instead, we explore the gross features of this interaction space to determine how prevalent these synergies are. We take a top-down approach, creating two new methods to measure the effects of removing genes from the full set. In the first, we develop a method to measure the transcriptional response to genetic perturbations across hundreds of thousands of cells revealing opposing classes of transcription factors regulating dendritic cell differentiation. In the second, we measure how millions of combinations of genetic perturbations impact the growth rate of two cancer cell lines.

Thesis Supervisor:
Aviv Regev, PhD
Professor of Biology, MIT; Core Member Broad Institute

Thesis Committee Chair:
Jeff Gore, PhD 
Associate Professor of Physics, MIT

Thesis Readers:
Alex K. Shalek, PhD
Pfizer-Laubach Career Development Assistant Professor, MIT

Joseph Lehár, PhD
Adjunct Professor of Bioengineering & Bioinformatics, Boston University; Executive Director, Computational Biology, MRL

Date and Time: 
Friday, May 4, 2018 - 3:00pm to 5:00pm

Broad Auditorium - Broad Institute, 415 Main St., Cambridge, MA