Grant: Project Grant

The research in this proposal is about a protein called BLTP1. Mutations in the BLTP1 gene cause ALKKUCS, or AKS, syndrome, which is a rare disease that causes miscarriage or neonatal death or (in surviving children) a variety of problems such as global developmental delay and joint laxity. Recently, it was discovered that BLTP1 is important for moving lipids (fats) inside the cell. We need the right kinds of lipids to be in the right places at the right time for our cells to work properly. When there is a sudden demand, the cell uses a special type of transporter to quickly move these lipids where they are needed. This transporter, which was discovered fairly recently and given the name "BLTP", is sometimes compared to a firehose, because it can carry a large amount of lipids to respond to a cellular emergency. However, we know very little about how the BLTP "firehose" is turned on and off, what makes the lipids flow, and how the flow of lipids is directed to the right place. Understanding how BLTP1 is regulated will be important for developing new drugs to restore lipid balance in disease. Studying the BLTP1 transporter is not easy, because it is very large and hard to work with. Luckily, this transporter is so important that similar proteins are found in other living organisms including bakers' yeast, which is a powerful model for scientific research. Excitingly, we have recently used this yeast system to find proteins that we think act as regulators to control the BLTP1 transporter. Our proposed research will determine if these proteins do in fact regulate the yeast version of BLTP1. If so, we will test if the related human proteins similarly control BLTP1 in human cells. If we can understand how the BLTP1 lipid transporter works and how it is controlled, it will help scientists to develop drugs that correct the issues caused by mutations in this gene.