The Broad's Genome Biology Program brings together a scientific community focused on deciphering the important information encoded in the human and other genomes, including genes and their regulatory controls. Understanding these components is fundamental to the study of human physiology in both health and disease.
Scientists in the Genome Biology Program share ideas and launch collaborative projects to tackle key challenges. The program also works closely with scientists in the Genome Sequencing , RNAi and Genetic Analysis Platforms . In addition, it collaborates with many other labs in the Harvard-MIT community and elsewhere.
The program consists of two main components: Genome Sequencing and Analysis, and Genome Regulation.
Genome Sequencing and Analysis
I. Major Scientific Areas
Cancer and Medical Resequencing
Genetic resequencing involves discovering mutations in targeted regions of the genome, with the goal of finding the causes of inherited and acquired diseases. The Genome Sequencing and Analysis Program works closely with the Medical and Population Genetics Program and the Cancer Program on these activities.
Microbial and Insect Vector Genomes
Microorganisms (including fungi, bacteria, and viruses) and insect vectors 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 insects and microorganisms to understand their genetic regulation, population variation, and specialized genomic mechanisms.
Vertebrate Genome Biology
One of the most powerful ways to understand the human genome is by directly comparing it with other mammalian and vertebrate genomes. Evolution tends to conserve the sequences of functional elements, allowing them to stand out above background. Broad scientists are leading a national program to sequence the genomes of more than 20 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. In addition, artificial or natural selective pressures have shaped key vertebrate genomes, including the dog and stickleback fish, allowing important traits and disease genes to be readily identified and studied in these organisms.
II. Research and Development Genome Annotation and Informatics
Genomic information is being collected at an unprecedented pace. A dedicated team of Broad researchers harnesses both experimental and computational approaches to analyze these data and to assign structural and functional information to key genome components.
Computational Research and Development
Sophisticated computational methods and tools enable scientists to effectively mine the data generated by genomic analyses. The Broad’s team of computational researchers develops and applies these approaches to help answer a vast array of important biological questions.
Molecular Biology Research and Develoment
Advances in DNA sequencing technologies are revolutionizing the depth, breadth and pace of biomedical research. Researchers in the Broad’s Genome Sequencing and Analysis Program use, develop and enhance these technologies for a range of laboratory applications.
Genome Regulation
Epigenomics
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 a variety of both experimental and computational approaches. Major projects include the genome-scale discovery of the binding sites of regulatory proteins and tracing the status of chromatin through cellular differentiation using advanced chromatin-mapping methods.
Transcriptomics
Applying genomic methods to analyze RNA enables scientists to identify novel genes and other functional elements across the human genome. Broad scientists are applying the latest computational and laboratory-based approaches to assemble a comprehensive catalog of the genome’s “working parts." One major effort focuses on the discovery and functional characterization of large intergenic non-coding (“linc”) RNAs, a novel class of genes with major regulatory roles.
Evolution of Gene Regulation
Comparative functional genomics employs the full arsenal of genomic techniques — from DNA and RNA sequencing to RNA and metabolite profiling — combined with biological experiments involving multiple species, all aimed at understanding how genes and gene regulation evolved. Broad researchers have developed a novel algorithm to reconstruct genes’ ancestries from genomic data and are now applying this approach to 15 different yeast species, and are also exploring ways to apply it to mammalian species.
Regulatory Circuits
The reconstruction of gene regulatory networks can shed light on their evolution as well as their roles in normal and disease biology. Broad researchers are working to predict and functionally dissect these networks on a genome-wide scale in variety of important cell types, including embryonic stem cells, hematopoietic cells, adipocytes and fibroblasts. The Genome Biology Program works closely with the Cell Circuits Program on these activities.
