Solving the mysteries of bioscience
Foundational Science Fuels Breakthroughs
Inspiring Next-Generation Scientists
string(564) "A two-channel confocal microscopy image showing the distribution of a common phospholipid, phosphatidylcholine (PC), in a human cell. The green channel shows the localization of all PC, which is found in every compartment. The magenta channel shows the localization of PC in trans-Golgi network vesicles, which has been selectively illuminated using genetically encoded protein sensors in that compartment. These sensors will be developed to visualize the transfer of lipids between organelles at contact sites. Credit: Itay Budin and Chris Obara, UCSD"
The Allen Distinguished Investigator program provides three-year grants between $1M and $1.5M to individuals and teams.
Our project is based on a new approach for lipid imaging using genetically encoded proximity sensors, which allows for quantitative fluorescence imaging of phospholipid pools in discrete organelles and sub-organelle compartments. When sensors are expressed on either side of a transmembrane domain, they measure the transbilayer distribution of lipids, which is not possible with other approaches. We will apply these sensors to measure lipid exchange across multiple membranes at contact sites between the ER and mitochondria, Golgi, or the plasma membrane. A complementary tool will be single-particle tracking (SPT) of individual organelle tethers and lipid transfer proteins, which can uniquely characterize contact architecture and dynamics. Using SPT, we will test models for how lipid sorting and exchange occurs at contact sites and if lipid asymmetry regulates their dynamics. The project will support further tool development and dissemination for these tools, including the establishment of multicolor lipid proximity imaging that can be used to identify new contact site regulators and new SPT modalities that will allow for imaging of lipid sorting into contact site zones.
This project is part of the 2024 Organelle Communication cohort
These researchers will explore a thrilling frontier in cell biology emerging from the discovery that organelles (cellular compartments) can directly connect to each other to exchange materials and information, forming complex and dynamic networks. Much of how these interactions occur remains unknown due to the profound challenges of observing rapid events on a nanometer scale. This cohort will pioneer new tools to directly observe and model the organelle ‘interactome’ across time, space, and cell type. Their findings will expand our understanding of core biological principles, with powerful implications for fields ranging from regenerative medicine to virology.
