Dr James Edgar

Our group focuses on the roles that endosomes and exosomes play in health and disease.

Endosomes are intracellular membrane-bound organelles that have several important roles. Endosomes regulate the trafficking of proteins and lipids between several pathways including the endocytic, secretory, recycling and degradative. As endosomes mature, proteins on the limiting membrane of endosomes can be sorted into domains that tubulate or vesiculate towards the cytosol for recycling. Conversely, proteins can be sorted to domains that subsequently invaginate inwards, away from the cytosol, where they form intralumenal vesicles (ILVs). Once an endosome has acquired ILVs, it becomes termed a late endosome, or multivesicular body (MVB). Trafficking a protein to an ILV has several functions; firstly it removes any signalling capacity of these proteins from interactions with the cytosol (this is especially important for downregulation of activated growth factor receptors), and secondly it packages proteins into vesicles that can be degraded or expelled from the cell.

MVBs have several potential fates. Fusion of an MVB with a lysosome forms a hybrid organelle, an endolysosome, where ILVs and their contents are degraded and recycled. Another fate of MVBs is that they may fuse with the plasma membrane where their ILVs are released into the extracellular milieu - these ILVs now become termed 'exosomes'.

Exosomes are suggested to be involved in intercellular (between different cells) communication and have been implicated in a number of physiological and pathological processes, including antigen presentation, cancer and neurodegeneration. However, the basic cell biology which underlies their biology is relatively poorly understood.  Our lab aims to identify the molecular machinery which governs the behaviour of endosomes and exosomes.

We have recently shown that in mammalian cells exosomes can be tethered to the plasma membrane of cells following their release. This tethering is dependent upon a protein called tetherin, which plays a similar role in the retention of a number of virions. This highlights the possibility that exosomes have roles in short-range communication, in addition to longer-range communications. Our group will focus on understanding how and why exosomes are retained by this tethering process.

Current areas of interest:

* Molecular mechanisms of exosome tethering

* The role of exosomes in MHC-II presentation

* PD-L1 trafficking

* Exosome transfer, uptake and delivery

* MT1-MMP trafficking

Lab members:

Dr Yağmur Yıldızhan (PDRA)

Mr Adam Bourke (PhD student)

Ms Trinity Eales (MPhil student)

Mr Jin Seok Lee (PhD student, co-supervised with Klaus Okkenhaug)

Previous lab members:

Dr Roberta Palmulli (PDRA)

Dr Hannah Jackson (PDRA)

Miss Anna Germon (PhD student)

Dr Panchali Kanvatirth (PDRA)

Funding

Wellcome Trust

The Royal Society

The Wellcome Trust Institutional Strategic Support Fund (ISSF)

Exosis inc, Florida (2022 - 2023)