Nutrient Signaling in budding yeast

It is a basic biological fact that all organisms interact with and modify the environment they live in, primarily in order to survive, and hence propagate their genes. In order to support the transmission of the DNA encoding an individual’s traits, it is necessary to create the cellular machinery that can support the interpretation of the information stored in said DNA, the translation of these instructions stored as (abstract) chemical sequences into biologically active molecules, which are finally required to execute the decoded instructions, which aid the individual in adapting to a given environment. All of these biological processes require raw materials in the form of nutrients in order to construct structural and functional components of the cell, along with their share of chemical energy in order for biochemical processes to occur at biologically realistic timescales.

The sum total of all ‘basic’ biochemical reactions that involve the building up (anabolism) of complex biomolecules, and their subsequent breakdown (catabolism) to simple chemical structures, is termed metabolism. The process of metabolism is central to cellular functioning, and influences the essential processes detailed above in complex ways. Moreover, metabolic reactions have been studied in great detail over the last half century (with the success of biochemistry is often displayed in impressive maps like this one). However, much less understood are the processes that

• regulate metabolic responses in cells
• couple metabolism with cellular processes like the cell cycle or apoptosis
• distinguish metabolic requirements of cells in unicellular and multicellular organisms.

The questions mentioned above are by no means novel. In fact, biologists have always been trying to piece together behavior at various levels (molecular, cellular, organismal…) in order to probe these phenomena.

In an attempt to probe the complexities of metabolic regulation, my research asks the question how do nutrients influence cell growth?. Cellular growth is a tightly regulated process, involving accumulation of biomass by anabolism, and eventually leading to DNA duplication and cell division. The relationship between cell growth and nutrient availability is of great interest in mammalian contexts such as cancer or liver function for various reasons. In light of the molecular and genetic complexity of mammalian systems, it is exciting to note that the unicellular model eukaryote Saccharomyces cerevisiae shares most of the important high level regulators of nutrient sensing and signaling with mammalian cells¹.

Thus, using yeast as my biological model of nutrient consumption and growth, I wish to study the regulatory pathways that aid cells in sensing and adapting to rapidly varying nutritional environments. To this end, I have developed a mathematical model of the nutrient signaling regulatory network², which I can simulate in various ‘nutrient conditions’ to predict cellular behaviors like cell growth, stress responses, autophagy, and cell division.

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(You can find the full graphic here)