Why Does the Transport of Molecules into the Nucleus Fail in Alzheimer?
We aim to understand how the neuronal protein Tau interferes with the transport of biomolecules across the nuclear envelope in Alzheimer’s disease. In Alzheimer's disease, Tau proteins can interact with entities of the nuclear envelope leading to impaired molecular transport in and out of the nucleus. In this project we aim to identify proteins that interact with Tau in the nuclear envelope. Tau can for example bind to proteins in nuclear pores, named nucleoporins, and we will try to identify which parts of Tau are relevant for this binding. Having identified the aberrant interactions of Tau with the nuclear envelope, we aim to find compounds and genetic modifiers that can prevent them and thus rescue the downstream transport deficits.
In this work we follow up on recent findings that identified aberrant interactions of Tau proteins with the nerve cell nucleus. We use a unique combination of proteomics, cell biology, protein biophysics and gene editing to understand how Tau proteins can disable transport across the nuclear envelope and how we could rescue these impairments in disease. We hope to understand Tau protein inflicted nuclear transport deficits in Alzheimer's disease and other tauopathies and develop an approach for interference with this pathological process.