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
Lead: Dr Eirini Meimaridou
The characterisation theme carries out proteomic studies and miRNA screening on the various projects in the Cellular and Molecular Immunology Research Centre (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.
Extracellular vesicle characterisation
Lead: Dr Paul Matewle
Our studies aim to compare the efficacy of microbial and animal cell derived vesicles in delivering anti-cancer drugs. Microorganisms release vesicles that are used to deliver toxins while cancer cells release vesicles that participate in cancer metastasis. This suggests that they are both effective in delivering their cargo.
Vesicles released by microorganisms that produce anti-cancer drugs will be used to deliver endogenously produced anti-cancer drugs they produce. Their efficacy will be compared with vesicles from microorganisms that do not produce anti-cancer drugs. The work will be extended to animal/human cell derived vesicles.
The factors that influence the production of anti-cancer drugs will be studied. Various species will be used as models to gain an insight into the link between vesicle and anti-cancer drug production. The ultimate aim of these investigations is to improve the delivery of anti-cancer drugs.
Collaborators in this programme include other CMIRC colleagues Dr C. Bax, Dr G McLean, Prof Palmer, Dr Sheelagh Heugh and Dr Samireh Jorfi. Other collaborators include Dr K White and an external collaborator Prof J Inal.
PhD students working in this area include
Gbemi Adeagbo: The anti-cancer activity of Purpureocillium lilacinum and Scopulariopsis brevicaulis vesicles during the production of anti-cancer agent’s leucinostatins and Scopularide A.
Preeth Sinavandan: The anti-cancer activity of Taxomyces andreane and Pestalotiopsis microspora vesicles during the production of anti-cancer agent paclitaxel.
Sajida Hashemi: The anti-cancer activity of Sorangium cellulosum and Bacillus thuringiensis vesicles during the production of anti-cancer agent’s epothilones and Parasporin
Developing new vaccinations for a silent killer
Dr Gary McLean, a Reader in Molecular Immunology at London Metropolitan University, worked as part of an international research team to investigate a new vaccine to combat a virus.