Spatial biology of membrane proteins

Most drugs in clinical use target membrane proteins.

Accumulating evidence shows that most membrane proteins are not uniformly distributed but localize to dynamic domains of nanoscale dimensions.

The nanodomain organization of membrane proteins enables the development of new types of multivalent drugs that target nanodomains instead of individual proteins.

However, to be able to engineer multivalent drugs with tailored affinity, specificity, and biodistribution, it is necessary to first map the composition and spatial organization of membrane protein nanodomains.In this research plan, we aim to develop new methods to map the spatial organization of membrane proteins at the single cell and tissue levels.

We have previously developed NanoDeep, a method that uses DNA sequencing as a readout for protein spatial organization, which does not have the limitations on the numbers of proteins that can be analyzed simultaneously.

Here, we propose to refine this method by enabling characterization of membrane protein nanodomains in single cells (NanoSiTE).

In addition, we will develop a method that introduces spatial organization information at the nanoscale in membrane proteomics analyses, NanoMaP. We will apply these tools to the characterization of insulin receptor nanodomains in different tissues.

This work has the potential to enable new insights into the biology of membrane proteins and form the basis for the development of nanomedicines targeting membrane protein nanodomains.