The success of DNA and RNA in, respectively, translating and transcribing their genetic information has as much to do with their physical structure and shape as with the nucleotides they contain. The Symposium on DNA and RNA Biology at the 2017 ASCB|EMBO Meeting will focus on some of the latest techniques being used to characterize these molecules and on how anomalies in their structures can lead to disease.
Angelika Amon, the Kathleen and Curtis Marble Professor of Cancer Research and HHMI investigator in the Department of Biology at the Massachusetts Institute of Technology, studies multiple aspects of cell growth and division and what happens to cells in which the process of chromosome segregation fails, mis-segregates chromosomes, and results in a condition known as aneuploidy. Because aneuploidy is a hallmark of cancer, determining its effects on cellular physiology is an area of intense investigation. In her Symposium talk, Amon plans to discuss aneuploidy’s effects on cells and how it relates to cancer. Through research in yeast, cultured mammalian cells, and mouse models, she has found that aneuploidy not only impacts gene expression but also affects virtually all aspects of the physiology of a cell, causing proteotoxic and oxidative stress. In her work on the question of how aneuploidy contributes to tumorigenesis, Amon found that aneuploidy causes genomic instability, which, she hypothesizes, could promote tumor evolution. Given the tumorigenic and mutagenic potential of aneuploidy, Amon’s lab more recently began to focus on mechanisms that eliminate aneuploid cells in the organism. She will discuss recent findings that indicate that aneuploid cells are cleared by the immune system.
Other speakers for the Symposium include Job Dekker, Joseph J. Byrne Chair in Biomedical Research, HHMI investigator, and co-director of the program in Systems Biology at the University of Massachusetts Medical School, and Carlos Bustamante, the Raymond and Beverly Sackler Professor of Biophysics at the University of California, Berkeley.
Members of Dekker’s lab have developed powerful molecular and genomic tools to study the three-dimensional structure of the genome inside the nucleus. For example, they invented Chromosome Conformation Capture (3C), which is used to detect physical interactions between genomic elements. With 3C, Dekker and others discovered that gene regulation is mediated by the three-dimensional organization of chromosomes that brings genes and their regulatory elements close together. To allow analysis of the folding of complete genomes they developed Hi-C, which combines 3C with deep sequencing, and Dekker and others are using it to generate comprehensive and unbiased long-range interaction maps of genomes. These maps will help to unravel how genome organization plays roles in gene regulation, in chromosome condensation and transmission, and in maintaining genome stability. Previously the Dekker lab found that the folding of the genome undergoes dramatic changes during the cell cycle. While the genome is folded in specific localized loops and a series of nested domains of various types in interphase, during mitosis all these structures are absent. Instead, chromosomes form rod-shaped structures that represent compressed arrays of stochastically positioned chromatin loops. In his presentation, Dekker will describe new insights his group obtained into how cells perform this remarkable task of folding, unfolding, and refolding chromosomes during the cell cycle.
Bustamante’s lab has been developing new single-molecule manipulation and detection methods, such as optical tweezers, single-molecule fluorescence microscopy, and super-resolution microscopy to help investigate DNA packaging into a bacteriophage; transcription; translation and protein folding; protein degradation via the protease ClpXP; mitochondrial fission; and catalysis-enhanced enzyme diffusion. His talk will focus on the use of ultra–high resolution optical tweezers to characterize the mechanochemical cycle of the motor responsible for packaging the DNA of bacteriophage Phi29 inside its capsid during viral assembly. Among other surprising results, the motor displays a division of labor in which only four of the five identical subunits perform a mechanical task whereas the fifth subunit fulfills a regulatory function. Moreover, the motor not only exerts force during packaging but also exerts torque, rotating the DNA molecule on its axis.
Symposium 5, DNA/RNA Biology, will be held Tuesday, December 5 at 8:00 am.