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Introduction
This course examines the role of cellular and genetic changes in disease, with examples. In each area the course emphasises a critical appraisal of existing literature on the subject, the laboratory methods available for investigation, and ideas for future research. The teaching is shared between leaders of research groups in the main building, histopathologists based at Addenbrooke's Hospital and members of the Departments of Genetics, Medical Genetics, Medicine and Oncology. All of the topics are considered as problems in cell and molecular biology rather than diagnostic clinical pathology, but all are highly relevant to human or animal disease.
The Course
The course is organised into 3 main modules that address the fundamental role of the genome in disease and the basic properties and functions of cells that play a part in disease processes.
Module I – Cell and Tissue Biology
This section examines basic aspects of cell and tissue biology. It considers regulation of the cell cycle and pathways leading to cell death that are important for the understanding of normal organogenesis. This leads on to the concept of stem cells and tissue morphogenesis through consideration of how signalling pathways determine cell fate.
Module II – Genome Approaches to Disease
This section focuses on the rapidly expanding field of studying disease mechanisms at the genomic level. It considers how the genome is organised, and its composition in relation to evolutionary and disease processes. This leads into comparisons of the strategies developed for physical and genetic mapping of loci contributing to single gene and polygenic diseases, the impacts of different classes of mutation on function, and the limitations on our current understanding of complex diseases. Lectures covering the effects of chromatin regulation and epigenetics address the importance of imprinting, de novo chromatin modifications in non-Mendelian disorders, and the current understanding of the developmental origins of disease, a limited transgenerational, but not genetically encoded, phenomenon.
Module III – The Molecular Biology of Cancer
A large section of the course is concerned with cancer and its relationship with regenerative processes, genetic alterations and viruses, and the tumour-host relationship. Somatic changes to the genome and the development of cancer are considered in some detail with respect to breast cancer, colon cancer and haematopoietic cancers. Several issues are addressed. (1) Oncogenes and tumour suppressor genes dealing with their identification and function. (2) The concept of chromosome and genetic instability. (3) The role of signalling in cancer. (4) Types of mutation in cancer. (5) Model systems.
Research Projects
Projects are in research groups at Tennis Court Road and at Addenbrooke's Hospital. Projects cover various aspects of, human molecular genetics and epigenetics, and cell biology and the molecular genetics of cancer. In addition, the Department has developed close links with colleagues in the Departments of Medicine, Paediatrics, Oncology and Medical Genetics where additional research projects are available.
Examples of Current/Previous Projects
2016/2017
- Characterisation of mitotic defects and expression of cell division proteins in oesophageal adenocarcinoma cell lines.
- Molecular Investigation of Lymphoma Development
- Elucidating the role of Roma and Gata3 in the DNA damage response.
- The genetic analysis of the Ashanti Dwarf pig
- Biomarkers in Barrett's oesophagus: assessment of aneuploidy and hotspot mutations for identifying individuals at high risk for developing oesphageal adenocarcinoma.
- Examining a potential Th17 cell of origin of Anaplastic Large Cell Lymphoma.
- Does over-expression of the oncostatin M receptor deregulate high-risk human papilomavirus oncogenes in cervical carcinoma?
- Epigenetic message in tumour stromaexosomes?
- Fertility-related genes evading cytoplasmic sharing during spermatogenesis.
- Analysis of canine transmissible veneral tumour response to vincristine chemoterapy.
- Epigenetic and Gene expression studies of candidate genes associated with stunted growth or periconceptional supplementation in Gambian children.
- Regulation of MITF by Fbxo7/PARK15.
- A histopathology-based phenotypic screen of Canine Transmissible Venereal Tumour.
- An investigation of the role of CD63 in programmed cell death during mammary involution.
- Does skin thickness and the presence of mutations that affect skin thickness affect Brachycephalic Obstructive Airway Syndrome severity in French Bulldogs?
- Investigation of circulating Tumour DNA as a biomarker for the diagnosis of Oeseophageal Adenocarcinoma Relapse.
- An Investigation of an Engineered 3D Anisotropic Collagen Scaffold Model Supporting Primary Tumour Growth and Tumour Cell Migration.
- Hsa-miR-1304-5p is a potent tumour suppressor in human neuroblastoma cell lines.
- Validating the FAM150 ligands for ALK in a PC3 model of ALK expressing Prostate Cancer.
- Dissecting the Cellular and Molecular Mechanisms of Primordial Dwarfism.
- Exploring the genetic landscape of Diffuse Large B Cell Lymphomas harbouring a MYC translocation.
- Investigation of nutritionally modifiable epigenetic correlates of positive and negative growth deviance in rural African fetuses and infants.
- CTCF association with the HPV16 genome regulates virus oncogene transcription and splicing.
- Initial validation of the ESCRT-III component CHMP4C as a target for ovarian cancer therapy.
- Novel role of Fbxo7 in fertility.