Research

Ongoing Research

All life forms have molecular systems to convert one form of energy to another. Our lab hopes to uncover the molecular mechanisms underlying these systems. Mainly, we focus on the mitochondria, which produce the primary energy molecules in cells, and the biological clock, which is associated with all major cellular processes and plays a role in energy homeostasis.

Currently, there are no cures or therapies for correcting mitochondrial dysfunction that underlies various diseases mainly because there is an incomplete understanding of basic mitochondrial biology. Though many aspects of mitochondrial dynamics are well understood, the molecular basis of cristae formation, maintenance, and dynamics remain unclear. Therefore, our lab works on deciphering the molecular details of cristae architecture, cristae dynamics in response to stimulus, and the cristae diffusion barrier. Ultimately, we would like to understand the origin of cristae and mitochondria.

Disturbances in the biological/circadian rhythm are also associated with a plethora of diseases. Based on studies using model systems, stimulus (such as light and energy requirements) is known to trigger activity within a transcriptional-translational negative feedback loop to alter organism physiology. However, the molecular details of mammalian photoreception and the cross-talk between the clock and metabolism remain unclear. Our lab is investigating the molecular details of the eukaryotic clock and its regulation by light and metabolism.

To address these above goals, we study the constituent protein molecules and their complexes with other macromolecules (proteins, RNA, and DNA) and small molecules (lipids, drugs, ATP, etc.) using structural biology tools such as X-ray crystallography, cryo-electron microscopy, and NMR spectroscopy. This is combined with solution-state biochemical and biophysical analyses to understand the conformational changes and protein dynamics. Our hypotheses from these in vitro studies are then tested at the cellular level.