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 is organised into 4 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 - Genes, Genomes and Disease:
The module focuses on the rapidly expanding field of studying disease mechanisms at the genetic level through identification of the genes involved, the genetic lesions they suffer, and the function of the proteins they specify in relation to the pathology of the disease(s) in which they are implicated. The module begins with a consideration of the strategies that have been developed for the analysis of complex genomes, specifically dealing with the question of the organisation of the human genome, techniques of genetic and physical mapping, the role of cytogenetics, and the key role of "positional cloning" in making accessible disease genes. The module then goes on to examine the molecular pathology of a number of important disease genes (such as cystic fibrosis), what we can learn from the development of mouse and other animal models for human genetic disease, and the role of genomic imprinting in disease.
Module 2 – Molecular Genetics and Pathology of Reproduction:
This module examines the role of the X and Y chromosomes in sex determination and male gametogenesis. This is then combined with a series of lectures on the clinical and molecular aspects of female infertility, ovarian development and oogenesis.
Module 3 - Defects in Cellular Growth and Differentiation - 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. Several issues are addressed. (1) The regulation of cell lifespan dealing with cell cycle kinetics, immortality, terminal differentiation, transformation and apoptosis. (2) Oncogenes and tumour suppressor genes dealing with their identification and function, tyrosine kinases, transcription factor oncogenes, the role of chromosome translocations in oncogene activation, and involvement of oncogenes/tumour suppressor genes in control of the cell cycle. (3) Tumour virology, examining DNA tumour viruses, human tumour viruses and retroviruses. (4) Familial cancer syndromes and hereditary cancer genes. (5) A final section on tumour biology where multistep carcinogenesis, invasion, metastasis, cell adhesion and host response are considered against what we understand of the genes involved in neoplastic growth.
Module 4 – Angiogenesis:
This module considers the mechanisms by which blood vessels are formed both during normal development and in pathological conditions. The lecture course covers the importance of angiogenesis for reproduction and foetal development, and the role of angiogenesis factors in cancers.
Projects are in research groups at Tennis Court Road and at Addenbrooke's Hospital. At Tennis Court Road there are groups conducting research into atherosclerosis, human molecular genetics (reproduction and the sex chromosomes), various aspects of the cell biology and molecular genetics of cancer, angiogenesis, and the immunobiology of pregnancy. 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
- Investigation of the porcine Y chromosome.
- Characterizing the role of Roma in mammary gland involution.
- Tracking Fluorescent Oncogenes in Living Cells.
- Studies of candidate genes for primary lens luxation in terrier breeds.
- Maternal infanticide in the pig: a genetic model for human puerperal psychosis?
- Identification of stem cells in the sub-mucosal gland ducts of the squamous oesophageal epithelium and development of Barrett’s oesophagus.
- Analysis of mutation expression in Breast Cancer.
- Mechanisms of Lymphomagenesis.
- How does over-expression of the oncostatin M receptor provide a selective advantage to cervical squamous cell carcinoma cells?
- Comparative and Functional Genomics of the Porcine Sex Chromosomes.
- Recurrent Chromosome Translocations in Breast Cancer.
- Stem and Progenitor Cells in Adult Lung Repair.
- Characterising the Proliferation and Differentiation of Primary Hematopoietic Stem Cells (HSCs) from Fbxo7 Null Mice.
- Investigation of Candidate Genes and Genomic Regions Involved in Maternal Behaviour.
- Mechanisms of Lymphomagenesis Research Group.
- Circulating miRNA for the Diagnosis of Oesophageal Malignancies.
- The Development of 3-dimensional Metastatic Breast Cancer Models.
- Optimising Target Enrichment for Next Generation Sequencing using the Fluidigm Access Array System.