Organization of Metabolism in the Hvorecny Group

Every cell rapidly responds to changing conditions by altering its flow of energy and molecular building materials to meet new demands. Cells can swiftly alter the flow of entire pathways in metabolism by triggering the reversible assembly of enzymes into micron-scale structures. These assemblies, many of which are filaments, modify the shape of constituent enzymes, tuning the rates of molecule synthesis and redirecting metabolic materials. While researchers recognize the importance of this cellular response, we lack basic principles describing how a cell organizes these assemblies and how assemblies diverge throughout evolution. We employ biophysical, biochemical, and cellular approaches to define the fundamental principles that physically organize metabolism the cell.

Current questions include:

1. How do metabolic enzymes combine regulatory mechanisms (filament assembly, post-translation modifications, isoform and gene co-assembly, small molecule activation and inhibition) to modulate metabolic output?
2. How do environmental signals trigger assembly and disassembly in vivo and what are the downstream effects?
3. How are these regulatory principles modified across the tree of life?

The spaciotemporal principles of metabolism are required to understand and develop treatments for metabolic diseases and disorders, including rare genetic diseases, metabolic dysregulation, and cancer. Assembly differences between humans and pathogenic organisms can potentially be leveraged for new antimicrobial strategies. In addition, the fundamentals of protein assembly can be applied to various design problems, which include creating green biofactories for molecules, developing enzyme-based chemical remediation platforms, and the de novo generation of new protein assemblies.