The Broad's Genome Biology and Cell Circuits program brings together a scientific community focused on deciphering the important information encoded in the human and other genomes -- including genes, regulatory controls and cellular circuitry. Understanding these components, controls and circuits is fundamental to the study of physiology in both health and disease.
Scientists in the Genome Biology and Cell Circuits program share ideas and launch collaborative projects to tackle key challenges. The program also works closely with scientists in the Genome Sequencing platform. In addition, it collaborates with many other labs in the Harvard-MIT community and elsewhere.
The program consists of two main components: Genome Analysis and Cell Circuits. The major areas of focus include:Genome Analysis
Mammalian Genomes.
One of the most powerful ways to understand the human genome is by directly comparing it with other mammalian genomes. Evolution tends to conserve the sequence of functional elements, allowing them stand out above background. Broad scientists are leading a national program to sequence the genomes of 16 mammalian species, with the goal of obtaining enough comparative information to recognize those functional elements that are conserved across all mammals. Comparing these sequences also reveals information about the evolutionary constraints and innovations in the class Mammalia .
Genome Regulation.
One of the great frontiers of genomics is identifying and understanding the regulatory elements that control the expression of genes. Deciphering this regulatory code involves both experimental and computational approaches. Current projects include: techniques for identifying conserved regulatory elements in promoters, UTRs and other genomic regions; large-scale discovery of the binding sites of regulatory proteins through chromatin immunoprecipitation; analysis of microRNAs and their target sites; and mass-spectrometric identification of proteins binding to particular DNA elements.
Microbial and Fungal Genomes.
Microorganisms (including fungi, bacteria and viruses) are both key model systems for genomics and important organisms for clinical medicine. Scientists in the Broad community are sequencing and analyzing the genomes of a wide range of microorganisms to understand their genetic regulation, population variation and specialized genomic mechanisms.
Cell Circuits Connectivity Map.
The Connectivity Map project seeks to connect diseases, genes and drugs by characterizing their interactions through the common language of gene expression. The project is assembling a database of 'cellular signatures', consisting of the genome-wide pattern of mRNAs induced by the actions of specific drugs, the inhibition of specific genes and the presence of specific diseases. Initial work has already identified several striking similarities that reveal surprising connections and validate this approach to understanding cellular physiology.
RNAi Consortium.
The recently discovered phenomenon of RNA inhibition (RNAi) provides a general technique to studying the function of any gene by creating a RNAi inhibitor specific for that gene. The Broad is the home of a public-private partnership, called The RNAi Consortium (TRC), which aims to create and disseminate validated RNAi against all human and mouse genes.
Immune Circuits.
A network of scientists in the Broad community is using RNAi to systematically investigate the development and regulation of the immune system, including B cells, T cells and dendritic cells. This work has important implications for both understanding basic immunobiology and for advancing clinical medicine.
