Doug Kellogg

Doug Kellogg Professor of MCD Biology
B.A., University of Wisconsin, Madison
Ph.D., University of California, San Francisco
Postdoctorate, University of California, San Francisco

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The goal of our work is to discover conserved, broadly relevant mechanisms that control cell growth and size.  Growth is a defining feature of life yet remains poorly understood.  Control of cell growth presents extraordinary challenges: the central processes of growth - ribosome biogenesis and membrane expansion - must be coordinated with each other, and the rates of each process must be matched to the availability of building blocks and energy derived from nutrients.  Control of cell growth also requires mechanisms that measure and limit growth, which ultimately define the size of cells. In multicellular organisms, growth must be tightly controlled to generate cells of diverse sizes and to prevent unrestrained proliferation of cancer cells.  The myriad forms of life produced by evolution are shaped, to a large extent, by mechanisms that control the extent, pattern and timing of cell growth.  Our current work is focused on these fundamental questions:

How do cells measure and limit their growth?  In all cells, key cell cycle transitions occur only when sufficient growth has occurred, which ensures that cells maintain an appropriate size.  Thus, cells must convert growth into a proportional signal that triggers cell cycle progression when it reaches a threshold.  The mechanisms by which cell growth is measured have remained deeply mysterious.  Our recent work suggests that the events of cell growth generate signals that are used to measure growth.  For example, we found evidence that the vesicles that drive plasma membrane growth deliver signaling lipids to the growing membrane, which activate protein kinases to generate a signal that is dependent upon growth and proportional to the extent of growth.  We have also identified signaling networks that read the growth-dependent signal and trigger cell cycle progression when it reaches a threshold.  Growth-dependent signaling suggests a simple and broadly relevant mechanism for measuring cell growth.  We are currently testing key hypotheses arising from our discoveries. 

What are the signals that control cell growth and size?  Observations reaching back over 60 years suggest that control of cell growth and cell size are closely linked.  For example, growth rate is proportional to nutrient availability, cell size is proportional to growth rate, and growth rate is proportional to cell size.  These relationships appear to hold across all orders of life, which suggest that they reflect fundamental principles, yet the underlying mechanisms have remained elusive.  We discovered that signals arising from a conserved TORC2 signaling network enforce proportional relationships between nutrient availability, cell growth, and cell size.  Our work suggests a model in which TORC2-dependent signals that set growth rate also set the threshold amount of growth required for cell cycle progression, which would provide a simple mechanistic explanation for proportional relationships between cell size and growth rate.  We are currently searching for the upstream signals that control the TORC2 network as well as the signaling outputs of the network that influence cell growth and size. 

How is control of cell growth and size disrupted in cancer cells?  Severe defects in control of cell growth and size are a nearly universal feature of cancer cells, yet little is known about the underlying molecular defects.  We have recently initiated new projects aimed at translating our discoveries in yeast into an understanding of how cell growth and size are controlled in vertebrate cells.  Our goal is to define conserved mechanisms that control cell growth and size, and how these mechanisms go awry in cancer cells.

Please follow this link to find the lab's publications in the National Library of Medicine's PubMed database.