Chromosome linearity is a potentially lethal problem – DNA ‘ends’ can be degraded or fused together, and this in turn drives genome instability and tumorigenesis. So why do eukaryotes bother with linear chromosomes? Our lab studies how telomeres, the unique structures at the ends of our chromosomes, not only avert chromosome degradation and fusion, but also choreograph chromosome movements and coordinate the completion of chromosome duplication with events at the nuclear envelope that trigger cell cycle progression. These studies have led to insights into what happens when telomere function diminishes (as it does with age or disease in humans) and have led us to new questions regarding centromeres (the chromosome regions that attach to mitotic spindles) and surprising instances of interchangeability between chromosome regions thought to be completely distinct.

Our research program seeks to understand the molecular logic governing the varying efficiency in RNA quality control and its impact on gene expression. Projects in the lab typically investigate variables that affect RNA surveillance using genome engineering, biochemical assays, and high-throughput sequencing. We also study the downstream consequences of failed RNA quality control in the context of a human muscle disease called facioscapulohumeral muscular dystrophy.

Students will team with a current lab member to study molecular mechanisms of epigenetics and gene regulation. Specific projects include: 1) structure/function studies to understand how epigenetic gene silencing spreads along the chromosome; 2) understanding how histone and RNA modifications are mis-regulated in human disease.

We are fascinated by the way RNA molecules “fold up” into complex 3-D structures, and how viruses use these RNA structures to “hijack” the cell’s biological machinery. MAP scholars in the Kieft Lab will work with other lab members to dissect how the structure of viral RNAs creates their function, or to help develop new RNA-based technologies. We use a variety of biochemical, structural, and biophysical methods that MAP scholars can learn.

Students in the Musselman laboratory will investigate the interaction of regulatory proteins with the nucleosome. They will gain experience in the expression and purification of recombinant proteins, nucleosome reconstitution, NMR spectroscopy, and other biophysical techniques. Their efforts will contribute to the overarching goal of the Musselman lab to better understand the fundamental principles underlying these genome regulatory events and help lay the groundwork for the development of targeted therapeutics.

Our genomes are packaged by proteins called histones. Parts of our genomes are packaged differently in different cell types, to allow for cells to express different parts of our genome and hence assume different cellular identities. We are interested in understanding how our genome packaging changes dynamically as cells change their identities and when cells respond to different stimuli. MAP scholars will develop methods to map genome packaging after perturbing processes that affect histone protein dynamics on the genome.

MAP Scholars in the Rissland lab will study a fascinating new area in developmental biology: what is the role of protein degradation in early embryogenesis? Using Drosophila melanogaster as a model system, they will investigate the developmental requirement for 5-10 protein decay enzymes as part of a larger genetic screen.

​Our laboratory seeks to understand how specific RNA molecules are trafficked to specific subcellular destinations. Toward that end, we often make use of transgenic proteins that are targeted to a specific location of interest. Potential projects include the creation and validation of such constructs. This would involve molecular cloning, cell culture, and fluorescent imaging.