Project 8: The stress response: a universal integrating module? (Rando) (#39-46)We studied chromatin structure and function by using a novel microarray to determine nucleosome positions at20-bp resolution. Chromatin plays a critical role in regulating any processes that take place on DNA, includingtranscription, replication, DNA repair, and chromosome segregation. Measuring chromatin structure at highresolution over genomic scales allowed us to describe a number of surprising features of yeast chromatin: 1)most of the genome is found in well positioned, rather than delocalized, nucleosomes16, 2) the pattern ofhistone modification is much less complex and much less instructive than advocates of the histone code hadproposed: the 12 different histone modifications occur in two grouped sets, transcription-independentmodifications marking promoters and transcription-dependent ones in the transcribed region17, and theacetylation of lysines on H4 primarily affects transcription by modulating overall charge18; 3) promoters have a200 base pair long nucleosome-free region where transcription starts16; this region is flanked by two wellpositioned nucleosomes that contain the H2A variant Htz1 and are hypo-acetylated at specific lysines19; 4)nucleosomes exchange rapidly at promoters and at known chromatin boundary elements; histone replacementrates over coding regions correlate with polymerase density20. In total, this work reveals that the chromatinstructure of yeast promoters is more stereotyped and dynamic than was previously thought. The technologicaladvances inspired similar studies in higher organisms, such as humans, where the analysis of chromatinstructure promises important insights into developmental processes, such as stem cell differentiation, and intodiseases with an epigenetic component, such as cancer. Oliver Rando, the PI, was a Bauer Fellow and is nowAssistant Professor of Biochemistry and Molecular Biology at U Mass Worcester.New project 8: Sociobiology at the genetic level: cooperation and conflict in microbes (Foster) (#47-50)Using microbes as models for sociogenomics, we investigate the genetic and genomic basis of two key socialtraits: biofilm formation in the pathogen Pseudomonas aeruginosa3*, and production of invertase, a foragingenzyme, in budding yeast40. Our goal is to characterize evolutionary cooperation and conflict in microbial socialtraits at both the genetic and phenotypic level, using a combination of empirical and theoretical approaches.Our first year has seen the successful development of four study systems: 1) Biofilm formation in thepathogenic bacterium P. aeruginosa. We find biofilm increases and gene expression patterns change whengenetically distinct strains of P. aeruginosa meet, consistent with a competitive response to the presence offoreign genotypes. This shows that one cannot fully understand microbial behaviors from single clone studies.2) An individual-based simulation of biofilm development. We find that slime production in biofilms can benefitthe slime-producers by pushing their descendents up into the nutrient- and oxygen-rich regions of the biofilm41.3) Secretion of invertase (which breaks down sucrose) and phosphatase (which converts organic phosphate toinorganic phosphate) by the yeast Saccharomyces cerevisiae as cooperative traits (in collaboration with A.Murray). 4) Flocculation as a social escape response in yeast (in collaboration with K. Verstrepen). This yearhas changed our perspective of these species by showing the central role that evolutionary conflict plays intheir behaviors. The notion that conflict drives microbial behaviors is central to both the correct interpretation oflab results, and to the treatment and avoidance of infections, which are nearly always associated with microbialgroup behaviors. Kevin Foster became a Bauer Fellow in 2005 and joined CMB in 2006.
| Westerman, Erica L; VanKuren, Nicholas W; Massardo, Darli et al. (2018) Aristaless Controls Butterfly Wing Color Variation Used in Mimicry and Mate Choice. Curr Biol 28:3469-3474.e4 |
| Bonham, Kevin S; Wolfe, Benjamin E; Dutton, Rachel J (2017) Extensive horizontal gene transfer in cheese-associated bacteria. Elife 6: |
| Hormoz, Sahand; Singer, Zakary S; Linton, James M et al. (2016) Inferring Cell-State Transition Dynamics from Lineage Trees and Endpoint Single-Cell Measurements. Cell Syst 3:419-433.e8 |
| Renn, Suzy C P; O'Rourke, Cynthia F; Aubin-Horth, Nadia et al. (2016) Dissecting the Transcriptional Patterns of Social Dominance across Teleosts. Integr Comp Biol 56:1250-1265 |
| Kastman, Erik K; Kamelamela, Noelani; Norville, Josh W et al. (2016) Biotic Interactions Shape the Ecological Distributions of Staphylococcus Species. MBio 7: |
| Lavrentovich, Maxim O; Wahl, Mary E; Nelson, David R et al. (2016) Spatially Constrained Growth Enhances Conversional Meltdown. Biophys J 110:2800-2808 |
| Battle, Christopher; Broedersz, Chase P; Fakhri, Nikta et al. (2016) Broken detailed balance at mesoscopic scales in active biological systems. Science 352:604-7 |
| Tamari, Zvi; Yona, Avihu H; Pilpel, Yitzhak et al. (2016) Rapid evolutionary adaptation to growth on an 'unfamiliar' carbon source. BMC Genomics 17:674 |
| Kim, Wook; Levy, Stuart B; Foster, Kevin R (2016) Rapid radiation in bacteria leads to a division of labour. Nat Commun 7:10508 |
| Muller, Nicolas; Piel, Matthieu; Calvez, Vincent et al. (2016) A Predictive Model for Yeast Cell Polarization in Pheromone Gradients. PLoS Comput Biol 12:e1004795 |
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