Organelle biogenesis is the process by which new organelles are made. Organelle biogenesis includes the process through which cellular organelles are split between daughter cells during mitosis; this process is called organelle inheritance. Membrane-bound organelles can also be generated through de novo synthesis where proteins and lipids both need to be inserted under precise control. Organelles often have their unique morphology that contributes to the specific function, often in ways that are poorly understood. We are particularly interested in the biogenesis of endoplasmic reticulum (ER), as it is the largest organelle in most eukaryotic cells and serves many essential cellular roles such as protein synthesis, lipid metabolism and calcium storage, etc. Currently we are asking questions such as: How do cells shape ER? How do they adjust ER size and function to physiological demand? How are ER inherited during cell division?

Autophagy is a highly conserved physiological process that degrades excess or damaged organelles, large protein aggregates and invading pathogens via the lysosomal system (the vacuole in plants and yeast). Autophagy can be non-selective bulk degradation, or selective. Selective autophagy recycles specific organelles, such as mitochondria and ER through receptor-mediated cargo selection according to the physiological needs. This capability makes selective autophagy a major process in maintaining organelle homeostasis, and the dysfunction of selective autophagy underlines many human diseases, including neurodegeneration, cancer, and metabolic disorders. We’re interested in studying the “selective” mechanism, and the current research focus is to identify specific autophagy receptors for different organelles such as nucleus, golgi, lipid droplets and peroxisomes.

We use multiple genetic systems in the lab to study organelle homeostasis, including two species of fission yeast (Schizosaccharomyces pombe and Schizosaccharomyces japonicus), the budding yeast Saccharomyces cerevisiae, and mammalian cell culture, as different systems have their unique advantages when addressing different questions. For example, the rod-shaped fission yeast S. pombe divides from the middle of the cells, and the organelles like ER redistribute to the division site during mitosis, providing a unique opportunity to study organelle inheritance. The other fission yeast S. japonicus has much bigger cell size, making it easier to be detected by light microscopy. It can switch from yeast to hyphal growth. S. japonicus hyphae remain mononuclear and undergo complete cell divisions but are highly asymmetric: one daughter cell inherits the organelle vacuole, the other the growing tip. Therefore, S. japonicus is a fun model system to study asymmetric organelle inheritance. We also purify our proteins of interest and use in vitro reconstitution systems (e.g., liposome reconstitution) to study their functions. Structural biology techniques will also be used to help us understand how membrane proteins work at the molecular levels.