Exosome Characterization in Immunity and Development - Biosciences, PhD (GW4 BioMed MRC DTP)

About
Supervisory Team: Dr Richard Chahwan (Lead)
Dr Rebecca Richardson (Bristol), Prof Steffen Scholpp (Exeter)
Location: Exeter, Streatham Campus

Project
Exosomes are cell-derived vesicles that are present in many and perhaps all biological fluids, including blood, urine, and cultured medium of cell cultures. Exosomes contain various molecular constituents of their cell of origin, including proteins and RNA. It is becoming increasingly clear that exosomes have specialized functions and play a key role in, for example, intercellular signalling and epigenetic inheritance. Exosomes can transfer molecules from one cell to another via membrane vesicle trafficking, thereby influencing the immune system, such as dendritic cells and B cells. Results suggest that exosomes may play a critical role in cell-to-cell signalling, by delivering protein and RNA molecules. For example, RNA in exosomes has been claimed to affect protein production in recipient cells. Conversely, exosome content may be influenced by molecular signals received by the cell of origin. Interestingly, cancer cells exposed to hypoxia secrete exosomes with enhanced angiogenic and metastatic potential. And more recently immunotherapy resistance against B cell lymphoma treatment has been attributed to exosome evasion.

This studentship has 3 main aims with a workload mostly based at the new Living Systems Institute-Exeter with some training/resources at Bristol. The prospective student will be identifying, purifying, and analyzing cell-type specific exosomes from mammalian and zebrafish origins. We expect this work to help attribute more defined physiological and pathological functions to these interesting novel epigenetic organelles.

Aim 1 – Year1/2: Isolate and sequence B cell exosomes from wild-type and immuno-compromised mice and zebrafish mutants. We intend to i) visualise B cell specific exosomes from various genotypes and assess their migration through imaging; ii) analyse/quantify these exosomes using flow cytometry; and iii) analyse their content and compare it to control to identify whether immuno-compromised organisms manifest differential exosomal content. Skills: biochemistry, animal studies, imaging, immunofluorescence, flow cytometry, and statistical analyses.

Aim2 – Year2/3: Sequence RNA species of exosomes from naïve and mature B cells from mice and zebrafish. As denoted below we intend to isolate different species from naïve and activated B cells, from both nuclear and exosomal sources. Skills: RNA purification and quantifications, next-gen sequencing, and computational and network analysis.

Aim3 – Year3/4: Mimic exosomal epigenetic signalling. We will treat B cells with key exosomal contents identified in aim2 to assess the epigenetic signalling effect of this treatment on immune system development. This could be followed by a battery of additional activation assays.

Skills: various epigenetic and immune assays.

Start date: October 2018

Most studentships will be 3.5 years full time or up to 7 years part-time, and can be longer where additional training is undertaken.


How to Apply
APPLICATIONS OPEN ON 25 SEPTEMBER AND CLOSE AT 17:00 ON 24 NOVEMBER 2017.

IMPORTANT: In order to apply for this project, you should apply using the DTP’s online application form. More information on the application process may be found here: http://www.gw4biomed.ac.uk/projects-2/for-students/

You do NOT need to apply to the University of Exeter at this stage – only those applicants who are successful in obtaining an offer of funding from the DTP will be required to submit an application to study at Exeter.