Overlaps between the fields of neurodegeneration and neuroimmunology

There are few examples of tractable overlaps between the fields of neurodegeneration and neuroimmunology. Yet, an immunological basis for a subset of patients with neurodegeneration would identify a group whose condition may be modified with the use of available immunotherapies. Dr Nath’s group have identified oligoclonal immunoglobulin bands in the cerebrospinal fluid of ~10% of patients with amyotrophic lateral sclerosis (ALS, also termed motor neuron disease). Further, endogenous retroviruses are observed to be activated in about 50% of ALS brains at autopsy. These observations mandate a search for the targets of the cerebrospinal fluid IgGs, to include retroviruses.

To identify antigenic targets, the DPhil candidate will use a variety of immunoassays established in both Dr Irani’s and Nath’s labs. These include B cell immunoglobulin heavy-light chain cloning, single cell RNA sequencing, western blotting, phage display screens and cell based assays.

In addition, these techniques will be applied to the cerebrospinal fluid of patients with Alzheimer’s disease to take an agnostic mass spectrometry based approach to identify antigenic targets of B cells and cerebrospinal fluid IgG in this cohort.

Overall, there will be excellent exposure to neuroimmunology and neuroinfection focused laboratories with the opportunity to learn multiple clinically applicable techniques to link common forms of neurodegeneration with a neuroinflammatory component.