our review on the maternal-to-zygotic transition is out! read all about how the genome activates

link here for the paper

We reviewed the literature of how the genome is activated following fertilization in vertebrates. Dave Jukam, with an assist from Ali Shariati and myself, did some heroic work pulling together the literature from frog, fish, mouse and human. Usually the model organisms frog and fish are considered separately from mammals. But, we were able to pull it together in what I think is a useful way. This was by far the most difficult review I have been a part of writing and it took over a year to put it together in a compact readable form. I'm proud of it and hope some ideas, like the use of various nuclear-to-cytoplasmic ratios to control events in early development, inspire future work revealing conserved principles of early development.

Our paper on budding yeast topologically associated domains is just out in PNAS

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.

Who we're with. What America should stand for (h/t Brad Delong)

our review of how cells exploit space and time to make better decisions is out in JCB! Happy new year!

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!

our paper on what makes a biological network modular is out in Cell Systems

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.