We focus on the mechanisms of protein metabolism - maintenance of the balance between the synthesis and degradation of proteins. We explore the regulation of translation, ubiquitin-proteasome system, chaperone network, and muscular exophers in proteostasis. However, we are sometimes intrigued by topics outside this list. In our laboratory, we use a combination of biochemical, microscopic, molecular genetics, and bioinformatics techniques, supported by mammalian cell assays and the nematode Caenorhabditis elegans.
Our research
Cellular adaptation to cold
To counteract cold, organisms developed various types of responses, ranging from cold avoidance to adaptation. The latter strategy is used by hibernating animals, which, in extreme cases, can survive subzero temperatures for many days. We focus on deciphering mechanisms altering the abundance and types of cellular messenger RNAs and proteins, as these kinds of molecules are critical for the live-or-die decision of the cell. As in some disease states, like stroke, cooling can facilitate a patient's recovery, understanding how cells adapt to cold has the potential to influence treatments of human disorders.
Mechanisms of muscular exopheresis
We discovered that large extracellular vesicles, termed exophers, that attribute in neurons and cardiomyocytes and carry damaged subcellular components, are released by muscles to support embryonic growth in Caenorhabditis elegans. Our results demonstrate that an exopher formation (exopheresis) represents a transgenerational metabolic/resource management system that supports embryos in utero. Currently, we investigate the mechanism of exopher formation and the regulation of exopheresis at the molecular level.
Stress-induced myosin folding and assembly mechanisms
Little is known about the regulation of muscle-specific response programs that coordinate protein quality control upon mechanical stress and in human disease. We established a Caenorhabditis elegans-centered array of experimental approaches for the in-depth investigation of myosin-directed stress induction mechanisms. The long-term objective of this project is to understand how protein folding and degradation networks are coordinated with the dynamics of myosin assembly, muscle integrity, and repair in the context of mechanical stress.
E3 ligase complexes in the integration of proteostasis and aging
From their synthesis to destruction, the fate of eukaryotic proteins is supervised by the ubiquitin-proteasome system (UPS). Cooperation of E3 ligases, essential components of the UPS that recognize damaged or misfolded proteins, can lead to the formation of alternative ubiquitylation structures that aid in directing substrate specificity. We investigate how specific E3 ligase pairs determine substrate recruitment and ubiquitin chain formation to coordinate proteolytic networks. Understanding the function and identifying the signals that coordinate the interaction between E3 ligases will provide information on how proteolytic networks are tuned to maintain cellular proteostasis in health and disease.
The regulation of methionine metabolism by the ubiquitin-proteasome system
Methylation is the modification that various cellular molecules, from nucleic acids to proteins to lipids, undergo. It is central to the regulation of many biological processes, including gene expression, signaling, protein synthesis and lipid metabolism. The long-term goal of this project is to understand how the ubiquitin-proteasome system modulates cellular methylation potential. Congenital methylation disorders are a group of rarely described and probably largely unrecognized disorders involving transmethylation processes. We model these human diseases on Caenorhabditis elegans to understand the molecular basis involved in the dysfunction of methylation pathway enzymes and their impact on physiology.
