Elucidating the transport of misfolded proteins across the blood brain barrier

GroupMolecular Bionics  and Molecular and cellular neurobiotechnology
Group leader: Giuseppe Battaglia (gbattaglia@ibecbarcelona.eu)  and José Antonio del Rio (jadelrio@ibecbarcelona.eu)

 

Research project

Neurodegeneration is the hallmark of several neurological disorders, including Parkinson, Alzheimer and other dementias. Often, this is triggered by the accumulation of misfolded proteins that aggregate into structures that induce inflammation and ultimately degeneration. α-synuclein is a key player in the pathogenesis of synucleinopathies, including Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. Amyloid-beta and Tau proteins are associated with Alzheimer’s, and in all these cases, the critical element in the pathology is how these molecules are transported across neurons and the blood-brain barrier (BBB). This latter comprises endothelial cells wrapped into vessels which in turn are coated by pericytes, astrocytes, and other glial cells. One of the most critical roles of the BBB is to shuttle metabolites in and out the brain, including α-synuclein, amyloid-beta, and tau.

Here we will combine the long-standing experience of the Molecular and Cellular Neurobiotechnology group (led by Jose Antonio Del Rio -JADR) on misfolded protein transport with the Molecular Bionics group (led by Giuseppe Battaglia -GB) experience in blood-brain barrier biology. We will study how brain endothelial sort different examples of misfolded proteins, using the recently reported syndapin-2 transcytosis (10.1126/sciadv.abc4397) and its relation with different disease states and ageing (https://www.biorxiv.org/content/10.1101/2020.07.12.199869v2). We will combine advanced imaging techniques with computational biophysics in both in vitro and in vitro models. We will explore the possibility that misfolded protein propagates like prions in and out of the brain using the BBB as the entry point. Such information will be critical to elucidate the pathogenesis of several disorders and inform new therapeutic approaches.

Job position description

We seek candidates either with physical and engineering background interested in neuroscience, or with life science background interested in biophysics. The student will

be trained in blood brain models, including 3D models and stem cells derived approaches. The students will also be trained advanced optical imaging techniques to track cellular and intracellular transport in live cells. Finally will also employ liquid phase electron microscopy to study the interaction between BBB receptors such as LRP1 and RAGE and misfolded proteins.