School of Molecular Biosciences

Dr Joseph V Gray

Understanding and Exploiting Eukaryotic Signaling Mechanisms using Yeast as a Model System.

We are interested in universal aspects of eukaryotic cell biology. Our research focuses on how the cell senses various internal and external signals to orchestrate proper cell morphogenesis, stress tolerance and entry into and exit from quiescence. We are also exploiting our understanding of yeast signaling to develop new tools for Synthetic Biology.

We employ a wide range of techniques as required, including molecular genetics, biochemistry and functional genomics. We study the simple model eukaryote, the budding yeast Saccharomyces cerevisiae, because of the un-paralleled power of post-genomic technologies in this organism, because of the universal nature of cell biology mechanisms and because of its biotechnological and industrial applications.

Nutrient Signaling: the TORC1 Pathway. We have long been interested in nutrient signaling and the entry into (and exit from) quiescence (Krause and Gray, 2002; Gray et al., 2004). TORC1 (Target Of Rapamycin Complex I) is a key regulator of cell growth and proliferation and a promising target for many potential and novel therapies including anti-cancer and anti-aging treatments.  TORC1 in both mammalian and yeast is regulated by nutrient state and prevents entry into quiescence. The mechanisms by which TORC1 senses nutrients are poorly understood but somehow involve the Rag/EGO complex.  We have recently clarified key aspects of the role of the EGO complex in regulating TORC1 (Evans et al., in preparation) and have, in collaboration with the Johnston/Singer lab at Dalhousie, identified potential and novel regulators of TORC1.

Morphogenesis and Stress: the Rho1 GTPase Pathway. The Rho1 pathway in yeast is tightly regulated to control proper cell morphogenesis during the cell cycle and during developmental transitions. The pathway is also regulated by external stresses such as heat shock (Gray et al., 1997) and is key to acquired stress tolerance. Most components are highly conserved between yeast and humans. We have studied and continue to study many aspects of this signaling pathway. For example, we have discovered post-transcriptional control of this pathway: a regulator of RNA metabolism and cellular lifespan, Mpt5p, modulates pathway activity by directly inhibiting expression of the Rho1 GAP (Stewart et al., 2007). We have recently revealed a new layer of complexity in Rho1 signaling: we have identified two novel dedicated co-factors for the Rho1 GTP exchange factors, the Ack1 and Rgl1 proteins, that are key to the proper spatiotemporal control of Rho1 activity during the cell cycle  (Krause et al., 2008, 2012).  

Synthetic Biology. We are interested in developing and exploiting novel tools for the engineering of yeast and eukaryotic cells as a chassis for Synthetic Biology applications. We are developing novel genome-engineering approaches using recombinases, with the Rosser and Stark labs, and are exploiting our expertise in cell signaling mechanisms to engineer tunable cell states and cell populations.