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Research

The goal of our research is to discover fundamental mechanisms that control cell growth and size in all eukaryotic cells.  Our work is focused on two key questions:

1.      How do cells measure and limit growth to control cell size?  In all cells, key cell cycle transitions occur only when sufficient growth has occurred, which ensures that proliferating cells maintain a specific size.  Thus, cells must convert growth to a proportional signal that triggers cell cycle progression when it reaches a threshold.  The mechanisms by which cells measure growth and trigger cell cycle transitions have remained deeply mysterious.  Our recent work suggests that vesicles that drive plasma membrane growth deliver phosphatidylserine to the growing membrane, which recruits conserved signaling proteins to generate a signal that is proportional to the extent of growth. Furthermore, we discovered a signaling pathway that could read the growth-dependent signal and trigger cell cycle progression when it reaches a threshold. Growth-dependent signaling suggests a simple and broadly applicable mechanism for control of cell growth and size.

2.      What are the signals that control cell growth and size? Observations reaching back over 60 years point to close relationships between control of cell growth and size.  Thus, 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 that 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 the proportional relationship between cell size and growth rate.

Together, our recent discoveries support hypotheses that could broadly explain how cell growth and size are controlled.  In our current work, we are testing key hypotheses arising from our discoveries, while also carrying out mechanistic analysis to further map the remarkable signaling networks that control cell growth and size.

 
 
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Publications

Modulation of TORC2 signaling by a conserved Lkb1 signaling axis in budding yeast. Alcaide-Gavilán M, Lucena R, Schubert K, Artiles K, Zapata J, Kellogg DR. Genetics. 2018 Jul 9. pii: genetics.301296.2018. doi: 10.1534/genetics.118.301296

Cell size and growth rate are modulated by TORC2-dependent signals. Lucena R, Alcaide-Gavilán M, Schubert K, He M, Domnauer MG, Marquer C, Klose C, Surma MA, Kellogg DR. Curr Biol. 2018 Jan 22;28(2):196-210.e4. doi: 10.1016/j.cub.2017.11.069

The duration of mitosis and daughter cell size are modulated by nutrients in budding yeast. Leitao RM, Kellogg DR. J Cell Biol. 2017 Nov 6;216(11):3463-3470. doi: 10.1083/jcb.201609114

A conserved signaling network monitors delivery of sphingolipids to the plasma membrane in budding yeast. Clarke J, Dephoure N, Horecka I, Gygi S, Kellogg D. Mol Biol Cell. 2017 Oct 1;28(20):2589-2599. doi: 10.1091/mbc.E17-01-0081

Fatty acid availability sets cell envelope capacity and dictates microbial cell size. Vadia S, Tse JL, Lucena R, Yang Z, Kellogg DR, Wang JD, Levin PA. Curr Biol. 2017 Jun 19;27(12):1757-1767.e5. doi: 10.1016/j.cub.2017.05.076.

Protein kinase C controls binding of Igo/ENSA proteins to protein phosphatase 2A in budding yeast. Thai V, Dephoure N, Weiss A, Ferguson J, Leitao R, Gygi SP, Kellogg DR. J Biol Chem. 2017 Mar 24;292(12):4925-4941. doi: 10.1074/jbc.M116.753004.

Wee1 and Cdc25 are controlled by conserved PP2A-dependent mechanisms in fission yeast. Lucena R, Alcaide-Gavilán M, Anastasia SD, Kellogg DR.Cell Cycle. 2017 Mar 4;16(5):428-435. doi: 10.1080/15384101.2017.1281476

Compact modeling of allosteric multisite proteins: application to a cell size checkpoint. Enciso G, Kellogg DR, Vargas A.
PLoS Comput Biol. 2014 Feb 6;10(2):e1003443. doi: 10.1371/journal.pcbi.1003443. eCollection 2014 Feb.

PP2A-Rts1 is a master regulator of pathways that control cell size. Zapata J, Dephoure N, Macdonough T, Yu Y, Parnell EJ, Mooring M, Gygi SP, Stillman DJ, Kellogg DR. J Cell Biol. 2014 Feb 3;204(3):359-76. doi: 10.1083/jcb.201309119.

Cks confers specificity to phosphorylation-dependent CDK signaling pathways. McGrath DA, Balog ER, Kõivomägi M, Lucena R, Mai MV, Hirschi A, Kellogg DR, Loog M, Rubin SM. Nat Struct Mol Biol. 2013 Dec;20(12):1407-14. doi: 10.1038/nsmb.2707. Epub 2013 Nov 3.

Mapping and analysis of phosphorylation sites: a quick guide for cell biologists. Dephoure N, Gould KL, Gygi SP, Kellogg DR.
Mol Biol Cell. 2013 Mar;24(5):535-42. doi: 10.1091/mbc.E12-09-0677. Review.

 

Doug Kellogg

Professor of MCD Biology University of California, Santa Cruz

1156 High St., 
342 Sinsheimer Labs
Santa Cruz, CA 95064

Office Phone: 831-459-5578
Lab Phone: 831-459-5659

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To support our research, please donate to the MCD Biology Fund and state that you would like your donation to support Kellogg lab research.  Alternative, contact Branwyn Wagman, Director of Development, at: bwagman@ucsc.edu.