Akbar Group - Generating extracellular vesicles for therapeutic Immunomodulation and building tools to determine their diagnostic potential.

ABOUT THE RESEARCH

The Akbar Lab is interested in defining the therapeutic and diagnostic potential of extracellular vesicles for immunomodulation and precision medicine in cardiovascular, metabolic, and inflammatory diseases. We have a particular interest in how endothelial cell derived extracellular vesicles mediate long range communication across organs and how we can capitalise on this signalling for targeted therapeutics and diagnosis.

We employ state of the art techniques in extracellular vesicle isolation and characterisation, using translational approaches of highly characterised clinical cohorts to derive hypothesis driven in vitro and in vivo studies using model systems. Where the technology doesn’t exist, we engineer tools to enable specific sub-populations of extracellular vesicles to be isolated and generate new approaches to exploit bio-engineered cells as factories for extracellular vesicle generation. 

 The focus areas of the lab are: 

1. Understanding which stimuli relevant to cardiovascular disease contribute to the generation and release of endothelial cell derived extracellular vesicles. We do this by using human and rodent cell culture of primary endothelial cells and immortalised lines. We employ CRISPR Cas-9 genome engineering and lentiviral vectors to modulate gene and protein expression, to generate high yields of extracellular vesicles for subsequent multi-Omics characterisation, in vitro and in vivo study.
2. Defining the immunomodulatory therapeutic potential of bioengineered extracellular vesicles. We are able to employ novel strategies to specifically target proteins to the surface of extracellular vesicles for immune targeting and simultaneously, incorporate bioactive molecules within their shells for delivery. These bioengineered cell lines provide a system to determine the therapeutic potential of extracellular vesicles for immunomodulation. 

We work collaboratively at the University of Oxford and internationally with leading experts to harness speciality knowledge and tools for our investigations into the diagnostic and therapeutic potential of extracellular vesicles.

Supervision may also be provided by Prof Paul Leeson, Prof Robin Choudhury and Ass. Prof Gillian Douglas.

TRAINING OPPORTUNITIES

The Group approaches all investigations by working inclusively with a diverse set of researchers to enable our translational investigations.  

Scientific training opportunities in the lab include but are not limited to:

     I.         Primary endothelial cell and immortalised cell line culture.

     II.         Peripheral blood neutrophil, monocyte or monocyte-derived macrophage cultures.

   III.         Extracellular vesicles isolation and characterisation 

   IV.         Nanoparticle Tracking Analysis (NTA)

    V.         CRISPR/Cas-9 genome engineering and PCR

   VI.         Lentivrial production 

 VII.         RT-qPCR 

VIII.         Western blotting 

   IX.         Transmission electronic microscopy (TEM) and cryo-TEM

    X.         Fluorescent microscopy and confocal microscopy.

   XI.         RNA-Arrays and sequencing, proteomics, lipidomics, metabolomics.

 XII.         Bioinformatics 

We actively encourage presentation skills development by regularly presenting work at local, national, and international conferences, meetings and through public engagement.

Students are encouraged to attend the MRC Weatherall Institute of Molecular Medicine DPhil Course, which takes place in the autumn of their first year. Running over several days, this course helps students to develop basic research and presentation skills, as well as introducing them to a wide range of scientific techniques and principles, ensuring that students have the opportunity to build a broad-based understanding of differing research methodologies.

Generic skills training is offered through the Medical Sciences Division's Skills Training Programme. This programme offers a comprehensive range of courses covering many important areas of researcher development: knowledge and intellectual abilities, personal effectiveness, research governance and organisation, and engagement, influence, and impact. Students are actively encouraged to take advantage of the training opportunities available to them.

As well as the specific training detailed above, students will have access to a wide range of seminars and training opportunities through the many research institutes and centres based in Oxford.

The Department has a successful mentoring scheme, open to graduate students, which provides an additional possible channel for personal and professional development outside the regular supervisory framework. We hold an Athena SWAN Silver Award in recognition of our efforts to build a happy and rewarding environment where all staff and students are supported to achieve their full potential.

PUBLICATIONS