Molecular Medicine
Our
research focuses on the study of a number of
human diseases, in particular cancer biology, viruses and infection, basic and
reproductive immunology, translational and clinical proteomics, bioimaging and
bioinformatics. We offer a
range of
undergraduate and
postgraduate degree courses in Biomedical Sciences. Individuals wishing to
specialise in an area of Molecular Medicine can apply to join either an MSc or PhD
degree programme.
Members of the Molecular medicine group
Dr Selwa Alsam, Dr Igor V Chernukhin,
Professor Richard J Cherry, Professor Nelson Fernández, Dr Andrew P Harrison,
Dr Richard D Jurd, Professor Elena Klenova, Dr Philippe Laissue, Dr Metodi Metodiev,
Professor John D Norton,
Professor Glyn Stanway
Key Research Topics:
Gene regulation and cancer
The work of our group is centred in the areas of regulation
and molecular mechanisms of tumourigenesis. We are investigating the biological
roles of two related proteins, CTCF and BORIS, in genetics, epigenetics and
disease, particularly in tumourigenesis, CTCF and BORIS belong to a group of
Zinc Finger transcription factors and share an identical DNA binding domain.
Although related, CTCF and BORIS have different functions. CTCF has properties
of tumour suppressor, whereas BORIS has features of an oncogene. CTCF is present
in various cell types, whereas BORIS normally is found only in the testis
but is activated in many cancers. Both CTCF and BORIS have properties as
biomarkers of breast, prostate and colorectal cancer; these studies are
currently being carried out in our laboratory in collaboration with clinical
partners.
Molecular mechanisms in
tumourigenesis
The interests of our group are focussed on the
role of the Id family of helix-loop-helix proteins in cell growth,
differentiation and tumourigenesis. The overall objective of our programme is to
understand, in molecular terms, the mechanisms through which the functions of Id
proteins are integrated in cell cycle control, tumour cell growth and cell
determination more generally. Several models of cancer including B chronic
lymphocytic leukaemia and colorectal adenocarcinoma are being used to evaluate
the ‘proof-of-principle’ of modulating Id function as an approach for
therapeutic intervention and for evaluating Id proteins as diagnostic tumour
markers. In conjunction with several collaborators, we also have interests in B
cell signalling and gene-based diagnostics in lymphoid malignancies and other
cancers, particularly B chronic lymphocytic leukaemia.
Poly ADP ribosylation and breast
cancer
There is compelling evidence of a relationship
between one of the post-translational protein modification, poly(ADP-ribosyl)ation,
and tumourigenesis. However, very little is known about the role of
specific targets of poly(ADP-ribosyl)ation which may be linked to tumour
development. This project aims to investigate the role of poly(ADP-ribosyl)ation
in breast cancer. We are currently developing the concept of poly(ADP-ribosyl)ation proteome
(PAR-proteome) in normal and breast tumours using high throughput proteomics
approaches. This research provides us with a new insight into the mechanisms of breast tumourigenesis.
Viral infection
Work is centred on the molecular biology of medically important viruses.
These include the enteroviruses which are a large group of RNA viruses and part
of the picornaviridae family. Important enteroviruses include the poliviruses,
the causative agents of paralytic poliomyelitis, and coxsackieviruses which can
cause a number of human diseases, including aseptic meningitis and heart
disease. Some enteroviruses have been implicated in the development of type 1
diabetes. Research interests also include the rhinoviruses, the major cause
of the common cold. We aim at improving our understanding of how viruses
replicate and cause disease to enable targeted design of vaccines/antiviral
agents.
Bacterial infection
Broadly our research interests are in all aspects of hospital-related
infections. We focus on the interaction of microorganisms such as, E. coli, the
causative agent of meningitis in neonates with the blood brain barrier and
encephalitis-associated mechanisms. Our other research interest is the study of the
role of aminopeptidases in the free-living amoeba, Acanthamoeba, the
causative agent of encephalitis and keratitis, pathogenicity and their possible
use as therapeutic targets. Currently, our team is working on the interaction of
MRSA, a leading cause of nosocomial infections, with Acanthamoeba. Our
area of interest is to study the ability of bacteria to be intracellular of
Acanthamoeba may be a factor in the evolution of environmental bacteria to
produce human infections.
Immunology and infection
Our focus is on understanding the membrane receptors involved in infection and
immunity; these include major histocompatibility complex-encoded receptors,
which are essential in antigen presentation and the handling of pathogens by
specialised cells of the immune system. We are investigating how gram-negative
bacteria infect cells and how macrophages respond to bacteria and what leads to ‘septic shock
syndrome' and multiple organ failure. This work is linked to the macrophage
specific receptor CD14 and other receptors, including the toll-like receptors of
the innate recognition arm of the immune system.
Reproductive immunology
We
study the relationship between the maternal immune system during pregnancy and
its influence in embryonic development and fetal tolerance. We have studied the
expression of MHC Class I genes in embryos harvested prior to implantation. We
found that mice strains devoid of MHC Class I gene products have a poor
reproductive fitness. This seminal observation has led us to the study of the
role of Class I molecules, HLA-G and HLA-E in human pre-implantation embryos and
during pregnancy. We are currently applying single cell bioimaging
techniques to the study of co-receptor associations and the
selective expression of MHC Class I in the fetomaternal
environment.
Translational and clinical
proteomics
Research is focussed on development and implementation of mass
spectrometry-based approaches for quantitative analysis of protein expression,
phosphorylation and protein-protein interactions in extracts isolated from human
cell lines, tumour tissues and other clinical specimens. These methods aim at
identifying biomarkers as tools for understanding health and disease as, for
example, in cancer. The projects are interdisciplinary and collaborative and
involve academics and clinicians from the UK, USA, Germany, and Australia.
Bioimaging and molecular medicine
A key component of the Molecular Medicine group is the use of state-of-the-art
bio-imaging technologies to study cells and tissues in health and disease. We
use imaging techniques to study cancer cells, DNA structures, and understand how
proteins in the body interact with pathogens such as viruses or bacteria, and
how these pathogens attach themselves to the cell membranes of healthy cells to
cause infection and disease. We pioneered the development single particle
fluorescent imaging techniques and confocal microscopy applications to study
receptors of the immune system and their cell membrane distribution and
dimerisation. Bioimaging is a core facility in the Department and has been
pivotal in the expansion of our new Biomedical Sciences BSc undergraduate and
Molecular Medicine and Biomedical Sciences MSc programmes, and in the training
of research students.
Bioinformatics
Modern biomedicine is increasingly dependent upon the analysis of large
data-sets. These include the so-called Omic technologies, such as epigenomics,
genomics, glycomics, metabolomics, proteomics and transcriptomics. The
application of these technologies enables whole-genome studies of a range of
biomolecules, each of which could be a key biomarker that discriminates between
health and disease. Although such technologies are potentially very powerful, as
equally important is the development of reliable tools for calibrating the
acquisition and interpretation of the data. The Essex bioinformatics group
specialises in improving the interpretation of large Omic data-sets, particularly
that for gene expression using RNA. This research is multi-disciplinary,
bringing together ideas from biology, informatics, physics and statistics.
Associated Centres