Research

Research Overview

The proficiency of cells to process information from the environment and respond appropriately to environmental signals; proliferate, differentiate or activate a specific response is dependent on robust and coordinated gene expression programs involving regulated transcription of thousands of genes. Our research focuses on elucidating how temporal binding of transcription factors; RNA binding proteins and chromatin regulators controls these responses. Indeed the production and regulation of RNA is so critical for cellular identity that more then a quarter of the genes in the mammalian genome are dedicated to control the RNA life cycle.

Charting the regulatory code controlling gene expression in mammalian cells is essential for interpreting non-coding genetic variation in human populations, for reprogramming and engineering cell states, and for understanding regulatory evolution. Transcription and chromatin factors bind to DNA in a combinatorial fashion to determine and modulate the amplitude and dynamics of gene expression. The elucidation of the genetic code and the set of rules of how information encoded in DNA is translated into proteins was perhaps one of the most important finding in modern biology. We focus on cracking the regulatory code, and the set of rules of how information encoded in regulatory DNA elements is translated into gene expression and cellular phenotype. Such knowledge has the potential to transform modern medicine and research.

The Amit lab studies how the hematopoietic system utilizes these sets of rules the regulatory code to differentiate cells into various professional immune cells that make up the immune system. Using state of the art high throughput single cell genomic approaches we explore: 1. The mechanisms of how expression of a single master transcription factor can reprogram various lineages to specific and functionally different cell types. 2. The genome of differentiated innate and adaptive immune cells is organized to invoke appropriate response through the expression of cytokines and affecter molecules to specific pathogen insults. 3. The involvement of Long non-coding RNA in regulating the gene regulatory program. We thrive to understand these sets of rules and how we can manipulate them to benefit human health.

To pursuit these goals in a systematic way we develop and apply massively parallel sequencing approaches coupled to automation and computational analysis to tackle these problems and expand our understanding on the organizational principals of mammalian genomes.