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The seminar is open to all. If you wish to meet with the speaker after the talk, please contact Nikolina Sekulic to arrange this: nikolina.sekulic@ncmm.uio.no
Abstract
The ability to synthesize large DNA assemblies has led to milestone achievements in prokaryotic systems and budding yeast chromosome biology. Chromosomes in mammals and many other eukaryotes control their own inheritance through an epigenetic locus: the centromere. The basic understanding of the molecular mechanisms that drive centromere identity/propagation has emerged over the last two decades, including work from my group that spans structural, genomic, and cell biological approaches.
Harnessing centromere epigenetics permits human artificial chromosome (HAC) formation but is not sufficient to avoid rampant multimerization of the initial DNA molecule that is introduced. In recent work in my lab, we describe an overhauled approach that efficiently forms stable, single copy HACs. Their single-copy nature is achieved by starting with a large (megabase) HAC construct that is sufficiently large to house the distinct chromatin types present at the inner and outer centromere. These HACs harbor full centromere function without the need to initially multimerize, thus permitting faithful chromosome engineering in the context of metazoan cells.
About the speaker
The longest standing goal of the Black Lab has been to understand how particular proteins at the centromere direct accurate chromosome segregation at mitosis and meiosis. His team defined the epigenetic centromere mark to be an octameric nucleosome containing the histone H3 variant, CENP-A, and contributed to the discovery and characterization of the biochemical pathway that propagates the centromere epigenetic mark through cell cycle-coupled CENP-A chromatin assembly; yielding the most prominent current molecular model for the self-propagation of centromeric chromatin. Black and his team used this understanding to develop a new type of artificial chromosome that removes a key barrier limiting mammalian synthetic biology efforts. In separate contributions, Ben and his team defined the process that activate the DNA damage sensing protein, PARP1, as well as how clinically-used small molecule inhibitors of PARP1 direct either release or retention on DNA breaks that relate to their effectiveness in killing tumor cells.
Ben has taught in or co-directed more than a dozen different courses in the Biomedical Graduate Studies (BGS) programs, School of Arts & Sciences, and Medical School. He has served on NIH review panels and as a reviewer for many national and international funding agencies. He is an Associate Editor of Science Advances and the Biochemical Journal and serves as a reviewer for >25 scientific journals, including Nature, Science, and PNAS. He has given invited lectures at numerous universities and meetings in the USA and in more than a dozen foreign countries. He has been recognized for his work with a fellowship from the American Cancer Society, a Career Award in the Biomedical Sciences from the Burroughs Wellcome Fund, a Rita Allen Foundation Scholar Award, the Michael S. Brown New Investigator Award, the Charles E. Kaufman Foundation Initiative Award, the inaugural Perelman School of Medicine Dean’s Innovation and Penn’s Discovering the Future Awards, the Stanley N. Cohen Biomedical Research Award, and the NIH Director’s Transformative Research Award.