Research Area: Disruptions in Protein Metabolism Cause Aging-Associated Diseases
We aim to understand the mechanisms underlying axonal degeneration, a chronic process that plays an important role in several neurodegenerative diseases. We study the function of several proteins involved in hereditary spastic paraplegia, a disease characterized by degeneration of the corticospinal axons. Ultimately, we aim to a better understanding of the pathophysiology of this disease, and to unravel possible therapeutic avenues.
ERLIN1 and ERLIN2 are homologous proteins of about 40 kDa that assemble in hetero-oligomeric or homo-oligomeric high-molecular weight complexes. ERLINs belong to the SPFH family of proteins, which have been proposed to organize membrane microdomains with distinct lipid and protein composition. Loss-of-function mutations in ERLIN1 and ERLIN2 genes have been found in patients affected by hereditary spastic paraplegia (HSP), a genetically heterogeneous neurological disease characterized by progressive degeneration of central motor axons. The ERLINs localize to the endoplasmic reticulum (ER), bind cholesterol, and promote ER-associated degradation of specific substrates, however how lack of ERLINs leads to HSP remains enigmatic.
In this project, we aim to investigate the molecular mechanisms by which the ERLIN complexes regulate ER morphogenesis by using a combination of candidate molecule approaches and of unbiased proteomics and lipidomics strategies. We will define the protein and lipid scaffolding functions of ERLINs in the ER . Finally, to investigate the role of the ERLIN complexes in vivo in the nervous system and assess if altered pathways identified in vitro are relevant for the degeneration of long motor axons, we will develop and characterize Erlin1-deficient, Erlin2-deficient, and double Erlin1/2-deficient mice.
The successful candidate must have a degree (master/diploma) in science (e.g. biology, biochemistry, chemistry or biotechnology) and a strong research interest in neuroscience and cell biology. Previous experience in cell biology or mouse genetics is an advantage but not a pre-requisite. Fluency in written and spoken English is required.