- Ph.D., Harvard University, 1996
The ultimate purpose of our research is to understand how cells regulate the shape and lipid composition of membranes to optimize organelle function.
My lab studies organelle biogenesis in the model organism S. cerevisiae with a combination of biochemical, genetic, and imaging approaches. Three projects in my lab include the following.
Intracellular lipid trafficking
We are working to identify proteins required for nonvesicular lipid trafficking in cells and to understand their role in organelle biogenesis and lipid metabolism. Previously, we focused on the role of oxysterol-binding protein homologs in sterol trafficking. More recently, we began studying phospholipid exchange between the endoplasmic reticulum (ER) and mitochondria and the role of close contacts between these organelles in lipid trafficking.
The ER forms a large, dynamic network that extends throughout the cell, with tubular and sheet-like domains. The reticulons and reticulon-like proteins help maintain this structure by stabilizing tubules and the edges of sheets. We are working to understand how these proteins shape the ER and what proteins they work in concert with. In addition, we are working to define the relationship between ER shape and ER function. For example, we recently found that ER-shaping proteins play a role in lipid exchange between the ER and mitochondria, perhaps by maintaining the shape of the ER at regions where these organelles come in close contact. In a second project, we are studying the role of the dynamin-like protein Sey1 in ER-ER fusion and lipid metabolism.
Formation and function of organelle contact sites
There is growing evidence that regions of close contact between organelles, often called membrane contact sites, are places where signals and small molecules are exchanged. Often, contact is between the ER and a second organelle. We are studying contacts between the ER and mitochondria, the plasma membrane, the Golgi complex, and the vacuole to understand how these sites form and what role they play in intra-organelle lipid transport and lipid metabolism.
Applying our Research
Defects in lipid metabolism and organelle biogenesis are associated with numerous diseases. Gaining insight into the basic processes in cells will help us understand how defects in them contribute to human disease.
Need for Further Study
Researchers have yet to study how the sizes of organelles are determined.
- Architecture of Lipid Droplets in Endoplasmic Reticulum Is Determined by Phospholipid Intrinsic Curvature.
- Choudhary V, Golani G, Joshi AS, Cottier S, Schneiter R, Prinz WA, Kozlov MM.
- Curr Biol (2018 Mar 19) 28:915-926.e9. Abstract/Full Text
- Lipid droplet and peroxisome biogenesis occur at the same ER subdomains.
- Joshi AS, Nebenfuehr B, Choudhary V, Satpute-Krishnan P, Levine TP, Golden A, Prinz WA.
- Nat Commun (2018 Jul 27) 9:2940. Abstract/Full Text
Research in Plain Language
Eukaryotic cells have organelles—internal structures that are somewhat similar to the organs in an animal. My lab is working to understand how cells make organelles in a process called biogenesis. We also want to understand how our cells regulate this process. We study organelle biogenesis in the model organism S. cerevisiae, also known as baker’s yeast. Because many aspects of organelle biogenesis are similar in all eukaryotes, what we learn in yeast should help us understand human cells as well.
We are currently focusing our research on the movement of lipids within cells, the structure of the endoplasmic reticulum (ER), and the formation and function of close contacts of the ER with other organelles.
The movement of lipids within cells
Organelles are membrane-bound structures in cells. These membranes are made of lipids and proteins. We are working to understand how cells move lipids between organelles and how these processes contribute to lipid metabolism in cells.
The structure of the ER
In most types of cells, the ER is the largest organelle. It forms a network of sheets and tubules that extend throughout the cell. We are working on understanding how this complex structure is generated and how the structure of the ER helps it function properly.
Formation and function of close contacts of the ER with other organelles
The ER makes close contact with other organelles. These sites are regions where signals and small molecules are exchanged between organelles. We are working to understand how they form and function.