Periodic Reporting for period 4 - CSUMECH (Cholesterol and Sugar Uptake Mechanisms)
Reporting period: 2020-01-01 to 2020-12-31
After the conclusion of the action, we have now shifted the frontiers significantly. We have elucidated the atomic details that pathway for sterol uptake in from lysosomes into the cellular membranes, and helped to pinpoint the mechanisms that govern this process. We have a deep and detailed understanding of sugar uptake, both in humans but also expanding to other eukaryotes, such as plants. The action has generated insights, based on the human sugar uptake system, that can have wide-ranging consequences for our ability model, control and argument sugar uptake in a range of organisms (humans, bacteria, plants).
We have published a model for sugar uptake and how this is regulated in humans and other sugar uptake systems in other organisms.
We have expanded on this to look at sugar uptake in plants and compare to the human system to understand the general mechanisms at play in this key pathway in eukaryotic metabolism.
Also using structural biology methods, we have elucidated how sterols are integrated into membranes via the action of a membrane protein NPC1/NCR1, using a hitherto undescribed tunnel to drive translocation of sterols past the glycocalyx. This result is a major breakthrough in the field and has been analyzed, and confirmed by numerous other groups afterwards.
We have described the first detailed atomic description of how sterol are integrated into the cellular membrane using the NPC1/NPC2 homeostasis system, redefining the molecular transport models in the field.