Metabolic sensing, "biochemical evolution" and cell fate
Depending on the specific metabolic context, or “metabolic state”, a cell can undergo different fates ranging from growth, division, differentiation and autophagy to a commitment to cell death. This metabolic state of a cell is controlled by available nutrients, which are sensed by specialized metabolic sensors. To understand cell fate decisions, we need to understand what makes some metabolites special and capable of controlling the decisions cells make. We also need to understand how these metabolites are sensed, and how this information is transferred to the eventual processes that determine the final outcome the cell takes (particularly protein synthesis and degradation).
We identify such metabolites and metabolic sensors, and the mechanisms through which these metabolites and metabolic sensors regulate cell fates. In particular, we are interested in the unique space amino acids occupy in metabolism, and their roles and abilities to drive different processes. We are interested in how they are made, and purposed for different ends. Since we are interested in this at a cellular level, we also explore how organelles signal between each other to coordinate metabolic responses, find proteins that enable this process of information transfer, and are also looking for core principles of metabolic sharing, and how cellular specialization and cooperation can be achieved within cell communities.
Our approaches are diverse, combining “traditional” biochemical, genetic and cell biological approaches with proteomics and targeted metabolomics. We use model systems to address these questions, especially (but not only) the budding yeast Saccharomyces cerevisiae to study pathways that are highly conserved across eukaryotes. We also work closely with theorists to build rigorous physical models to better explain (or provide new insight) to our findings. We hope our discoveries of new mechanisms of nutrient sensing, metabolism and translation regulation will lead to a foundational understanding of how metabolism regulates processes such as regeneration, cell proliferation, differentiation and cell survival. More broadly, we are trying to re-imagine metabolism and biochemistry as questions in cell biology, and possibly evolution, and are trying to understand what "metabolic costs" actually mean to a cell, and putting real molecules and quantities to this term.
You can read more about our published research in our publications page.
Current projects in the lab include:
i) Metabolites and cell fate switches: Understanding how specific metabolites cause specific transformations, which control different cellular outputs or fates.
ii) Metabolic sensing: Discovering new modes by which cells sense specific metabolites, and regulate outputs. We extend these studies to how these metabolites regulate signaling, and cell growth.
iii) Metabolic sharing, cooperation and conflict: Defining principles to describe metabolic determinants of cellular cooperation in (microbial) cell communities. We are particularly interested in how isogenic cells differentiate into specialized communities, and in determining both the nature and mechanisms of achieving resource sharing.
Some of these studies also require new tool building and engineering, or developing new methods or devices, such as quantitative metabolite measurements using mass spectrometry, or novel microfluidic devices, or new imaging systems, or software, which we integrate into our research along the way.
Funding and support: