Centre of research
Cellular Molecular and Immunology Research Centre (CMIRC)
The Cellular Molecular and Immunology Research Centre (CMIRC), founded in 2009 by Prof J Inal, consists of four research themes made up of 14 internal research staff, 12 PhD students and numerous external collaborators from multidisciplinary backgrounds within biomedicine. This community of scientists, together with industrial partners and clinicians, is comprised of several unique groupings with a focus on understanding and harnessing cellular, molecular and immunological properties of biological systems to further research and knowledge in biomedicine.
Our aim is to use an understanding of cellular and molecular biological processes, immune responses to viruses and cancer cell biogenesis/metastasis, to develop effective interventions for human diseases. A common theme is the characterisation of extracellular vesicles (EVs) in these systems and their use as targeted therapeutic agents. The current research themes therefore are: cancer (novel cancer immunotherapies and sodium/calcium ion channels in cancer), immunity to viral infections (cytomegalovirus, coxsackievirus and rhinovirus), molecular and cellular medicine (EVs characterisation/application), and tissue remodelling.
One of the strength of CMIRC’s approach is that it is involved directly from the basic laboratory experimentation through to clinical development, aiming to make its research findings translational. It is therefore actively involved, through collaboration with industry and other pan-European laboratories and research centres, in bringing about clinical applications from its findings.
CMIRC is dedicated to collaborating with and training researchers from undergraduate to PhD level and to providing opportunities for postdoctoral researchers. Visiting scientists are always welcome, as are interns that wish to see whether scientific research is for them and to expand their technical repertoire. CMIRC also aims to increase awareness of novel therapeutic approaches to disease and has been a pioneer in extracellular vesicles research and of its potential application; our approach is to make potential future students aware of opportunities in research through seminars, exposure to expert scientists and encouraging participation and discovery. We are also excited that the research conducted has unearthed new scientific information and disease treatment possibilities, many of which have now entered the current teaching and learning curriculum and are provided in modules that form part of the BSc and MSc degree programmes in Biosciences within the School of Human Sciences.
The CMIRC image is the modelled peptide structure of the immunologically important part of Schistosoma Tetraspanning Orphan Receptor (formerly Trispanning Orphan Receptor) discovered in 1997 (Inal, J (1999) Schistosoma TOR (Trispanning Orphan Receptor), a novel, antigenic surface receptor of the blood-dwelling, Schistosoma parasite. Biochim. Biophys. Acta 1445, 283-298; Inal, J and Sim, RB (2000) FEBS Lett. 470, 131-134; J Immunol. 168, 5213-5221; J. Immunol 170, 4310-4317) and more recently shown to be a prime vaccine candidate against Schistosoma mansoni (Lochmatter, C et al, (2012) Clin. Exp. Immunol. 170, 342-357).
Lead: Dr G McLean
Antibodies, vaccine development and extracellular vesicles.
Studies aim to establish correlates of protection for viral diseases, the role of antibodies in viral neutralisation and strategies to design better vaccines.
We are characterising and producing recombinant human antibodies to the AD-2 epitope of human cytomegalovirus (HCMV) and determining the specifics of human IgG and IgA in protective immune responses. These could find utility as biotherapeutics for HCMV infections.
We are developing a novel subunit vaccine for rhinoviruses (RVs) and characterising antibody and T cell responses that are broadly cross-reactive. Recent studies have identified novel antigenic determinants of the rhinovirus capsid and we will produce and further characterise monoclonal antibodies to these epitopes.
Our studies continue in the area of host microvesicles (MVs) and rhinovirus (RV) infection and aim to characterise the kinetics, structure and contents of MVs released from cells following RV infection and to determine their role in virus spread. This is a novel and untested hypothesis for the non-enveloped RV, although previous research has identified a role for MV’s in the infection of cells by the related non-enveloped virus coxsackie type B and important human enveloped viruses including hepatitis C virus, human immunodeficiency virus, Epstein-Barr virus and human cytomegalovirus.
The role of intracellular antibody virus neutralisation via the molecule TRIM21. New studies that address a novel mechanism of antibody neutralisation and applicability to RV neutralisation.
Lead: Professor Chris Palmer
Our projects include:
- Inhibition of microvesiculation to limit drug efflux in prostate cancer. This is coupled to another project on using microvesicles (including those derived from stem cells) as targeted drug delivery vehicles in cancer research.
- Use of prostate cancer-targeted microvesicles delivering both chemotherapeutic drug and inhibiting subsequent microvesiclation.
- The role of microvesicles in EMT transdifferentiation in prostate cancer.
- HPV/EBV and microvesicles in prostate cancer.
- Microvesicles and complement inhibiting peptides that break tolerance by inhibiting iC3b-CR3 interaction, thus allowing maturation of dendritic cells; Novel immunotherapeutic approaches in prostate cancer therapy.
- Transdifferentiation and dedifferentiation in monocytic leukaemia.
Molecular Cellular Medicine
Dr Eirini Meimaridou (Principal Lecturer)
Dr Sheelagh Heugh
Dr Gary McLean (Reader)
Dr Daniel Stratton (Senior Lecturer)
Dr Paul Matewele
The characterisation theme carries out proteomic studies and miRNA screening on the various projects in CMIRC. Following on from Dr. Stratton’s PhD research MCRG is continuing the characterisation of microvesicles released upon stimulating cells (sMVs) and those constitutively release (cMVs) with a particular focus on erythrocyte microvesicles. We also collaborate with Dr. Scott-Wildman of the Medway School of Pharmacy to study microvesicles in renal transplant recipients (RTRs) who are particularly susceptible to recurrent urinary tract infection.
Dr. Dan Stratton (Lecturer)
Prof. Chris Palmer
Dr Bhaven Patel
Mr Christopher Chamberlain
Dr Bruno Da Silva
Dr. Chris Bax (Principal Lecturer)
Dr Dan Stratton has been engaged in characterising microvesicle biogenesis. This unique work lead to the discovery of two distinct microvesicle subtypes that are identifiable from one parent cell type depending on their pathways of biogenesis. The research involved describing their distinct properties such as protein profile, size and receptor expression and how this relates to their biogenesis. This research also discovered for the first time that microvesicles carry calcium as cargo.
Applying the field of microvesicles to tissue regeneration, the RMRG aims to better understand the molecular and biochemical principles underling planarian tissue redistribution, regeneration and apply them to Human medicine.
- To elucidate the role of microvesicles in planaria and Human regeneration.
- To identify Human homologues to protein expression during planaria regeneration and apply the mechanisms of their expression to human cells.
- To discover the processes governing cellular redistribution according to their scale.
- To develop and employ the necessary tools to conduct the research.
Microvesicles have been shown to be implicated in a wide variety of cellular functions including, apoptosis, differentiation, proliferation and metastasis.
RMRG will be conducting tissue repair work using the 3D printing process. In conjunction with our other research interests this offers exciting possibilities into Human regenerative medicine.