Members of the Structural and Functional Genomics research program focus upon three specific thematic areas: (1) Genome Instability; (2) Human Cancer Genetics, and; (3) Systems Biology. Each theme represents an area in which members either have considerable strength upon which to capitalize, or one that we recognize as being important and wish to build upon existing scientific strengths. While these areas may seem different, they all share a common interest in the use of genetics. In fact, a number of members participate in more than one research area.
Genome instability has grown to be a key question in cancer biology. Virtually all cancers are impacted by genome instability, if only because virtually all cancers accumulate genome rearrangements and mutations. These genome rearrangements and mutations alter gene functions that then drive the development and progression of cancer. Furthermore, considerable evidence exists that defects leading to a more generally unstable genome drive the development and progression of cancer by increasing the rate at which critical genome rearrangements and mutations occur. However, our overall knowledge of the pathways and mechanisms that maintain the stability of the genome is limited. Work conducted by members in this program directly impact on the topic of genome instability. Our work employs a broad range of methods including: genetics; cell biology; biochemistry; structural biology; and mass spectrometry based proteomics. These efforts utilize a breadth of experimental organisms including S. cerevisiae, C. elegans, Xenopus, human cell based systems and mutant mice to widely address basic questions about genome instability.
Human Cancer Genetics
Cancer genetics is a broad research area that includes such diverse areas as: 1) the use of human genetics to discover genes in which inherited defects cause cancer susceptibility and in which somatic defects contribute to cancer development and progression; 2) the analysis of population genetic variation in cancer susceptibility, prognosis and response to therapy; 3) the use of clinical populations to investigate a diversity of genetic questions ranging from genetic counseling methods to the effect of genetic defects on prognosis; and 4) the use of mutant mouse models and mammalian cell based systems to investigate the mechanistic implications of cancer-relevant genetic defects. The human genetics efforts are focused on two key areas of human cancer genetics: the use of human genetics in cancer gene discovery and the analysis of population genetic variation. Work involves numerous approaches including: modern versions of the linkage/association studies and positional cloning paradigm; candidate gene and specific gene evaluation within selected clinical populations, sometimes involving high-throughput DNA sequencing; population-based SNP association studies; and development of biostatistical methods for analyzing large genetic data sets.
Building upon the work carried out by members of the Structural and Functional Genomics research program, the systems biology effort in Structural and Functional Genomics is focused on the DNA damage response utilizing model organisms and a diversity of approaches including microarray methods, proteomics, and classical genetics.