Paper is available here. According to the significance statement, which we recently wrote: In metazoans, topological domains are regions in the genome that more frequently associate with themselves than with neighboring regions. These domains are important for regulating transcription and replication. However, topological domains were thought to be absent in budding yeast. Thus, we did not know the degree of conservation of topological organization and its associated functions. Herein, we describe the existence of topologically associating domains in budding yeast and show that these domains regulate replication timing so that origins within a domain fire synchronously. Our work showing conservation in budding yeast sets the stage to use yeast genetics to interrogate the molecular basis of the topological domains defining genome architecture.
Check it out at http://jcb.rupress.org/content/early/2017/01/01/jcb.201609124
Oguzhan and I focus on MAPK kinase pathways and review recent work showing how the cell exploits both space and time to make better, more accurate decisions. Arguably, this examination has progressed furthest in the context of budding yeast, which we focus on. It is an exciting time as we move beyond knowing the majority of components in particular signal pathways to understanding how the cell uses all the components together in their physiological context to sense incoming signals, process them, and use that information to make crucial decisions. It has been quite some time coming, but finally, I think it is safe to say that the initial promises of systems biology writ large are coming to fruition (although not through any short cuts, but through long, hard empirical work, informed by theory). In any case, I hope you all enjoy it. Happy new year!
Here is the link (click here). Synopsis: Biological networks are highly complex, with many interconnected parts. Yet, network analysis based on small modules has proven highly effective in understanding physiological function. Our paper aims to address, at least in part, why this is the case. We show, through an analysis of the network comprising the cell cycle and pheromone pathways, that bistable switches are part of the answer. In this case, if the cell cycle switch is off, then the pheromone pathways measures the extracellular concentration unperturbed, even when the cell cycle pathway is pushed up to the bifurcation point. However, everything changes when the switch is flipped, as the cell cycle dismantles the pheromone pathway. Thus, the pheromone sensing module is unperturbed by the cell cycle in early G1 and so can be accurately modeled without including the cell cycle phase variable. Anyway, check it out. I think this subject of why motif analysis works is worth exploring since it is really not a priori obvious that it should once you think about how interconnected cellular networks are.
From left to right, Rob Fisher, Stacey Blaine, Mardo Koivomagi, Jim Watson, Elizabeth Lewis, Kim Nasmyth, unknown, Amy Ikui, Clayton Schwarz, Bruce Futcher, Jon Turner
It was fun, and, I think, the first time there was an entire session on the subject of how cell growth, or cell size, acts to trigger division. The focus of several groups is now on the question of how cell size impacts the synthesis of different proteins differentially so that increased size leads to a change in the ratio of cell cycle activators to cell cycle inhibitors. Progress is happening now! Now, we just need to new meeting to talk about this at...