Edgar Group

Our Research

Our research focuses on ultrastructural cell biology, particularly the regulation, behavior, and fate of small vesicles within and between cells. Specifically, we aim to unravel the biology of endosomes and exosomes, with a key interest in understanding why cells tether exosomes to their plasma membranes and the functional roles of these tethered exosomes in various biological processes.

Exosomes are small vesicles released from cells. They originate as intraluminal vesicles within endosomes and are termed exosomes once the endosome fuses with the plasma membrane. As a postdoctoral research associate, James made the key discovery that exosomes often remain attached to the cell surface, clustering in patterns that resemble the restriction of enveloped viruses. Our studies revealed that this retention is mediated by the antiviral restriction factor, tetherin.

The primary focus of our lab is to investigate how and why cells retain exosomes on their surface. We have found that many cells naturally tether exosomes, and we are working to understand the function of these tethered vesicles in both health and disease. Current projects explore their roles in antigen presentation, metastasis, cancer immune evasion, and mast cell biology. Our approach integrates a variety of biochemical and molecular techniques, with extensive use of light and electron microscopy.

Current Projects

• Examining the role that exosomes and tethered exosomes play in antigen presentation (Mr Jin Seok Lee)
• The role of tethered exosomes in breast cancer metastasis (Dr Roberta Palmulli)
• The molecular mechanisms of exosome tethering (Dr Yagmur Yildizhan)
• Exosome tethering by EBV-transformed B cells (Mr Adam Bourke)
• Endocytic trafficking of PD-L1 (Ms Trinity Eales)
• Exosome fate (Dr James Edgar)

Recently published work from the Edgar lab

• Bioengineered small extracellular vesicles deliver multiple SARS-CoV-2 antigenic fragments and drive a broad immunological response - Jackson et al., 2024
• Tetherin antagonism by SARS-CoV-2 ORF3a and spike protein enhances virus release - Stewart et al., 2023

Recently published collaborative work

• The SARS-CoV-2 protein ORF3c is a mitochondrial modulator of innate immunity (Firth, Smith, Edgar labs, 2023)
• Establishing SARS-CoV-2 membrane protein-specific antibodies as a valuable serological target via high-content microscopy (Peden lab, 2023)
• Multi-omic approach characterises the neuroprotective role of retromer in regulating lysosomal health (Cullen lab, 2023)
• Altered subgenomic RNA abundance provides unique insight into SARS-CoV-2 B.1.1.7/Alpha variant infections (de Silva lab, 2022)
• Ultrastructural insight into SARS-CoV-2 entry and budding in human airway epithelium (Burgoyne lab, 2022)
• Organelle tethering, pore formation and SNARE compensation in the late endocytic pathway (Luzio lab, 2021)
• Exploiting Connections for Viral Replication (Eden lab, 2021)
• De Novo VPS4A Mutations Cause Multisystem Disease with Abnormal Neurodevelopment (Reid lab, 2020)
• A dysfunctional endolysosomal pathway common to two sub-types of demyelinating Charcot-Marie-Tooth disease (Roberts / Edgar lab, 2020)
• OPTN recruitment to a Golgi-proximal compartment regulates immune signalling and cytokine secretion (Buss lab, 2020)

On-going collaborations

• Hayward, McGovern, Okkenhaug, Blagborough, Laman, Ferguson, Artavanis-Tsakonas (Pathology)
• Dickens / Rawlins, Cox (other departments)
   

Team composition

Dr James Edgar - Group Leader

Dr Yagmur Yildizhan - Postdoctoral Research Associate

Mr Adam Bourke - PhD student

Mr Jin Lee - PhD student

Previous lab members:

Dr Roberta Palmulli - PDRA

Dr Hannah Jackson - PDRA

Dr Panchali Kanvatirth - PDRA

Ms Trinity Eales - MPhil student 

Previous undergraduate project students:

Noah Palombo, Nasyen Madhan Mohan, Zahra Khwaja.

Group Members 

Group Leader - James Edgar