NST Part II Pathology - "Single Subject"
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 5 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 disease processes such as cancer. This leads on to the concept of stem cells and tissue morphogenesis through consideration of how signalling pathways determine cell fate.
Module II – Genome Organisation and its Regulation:
This section focuses on the rapidly expanding field of studying disease mechanisms at the genetic level through identification of the genes involved. It considers 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 emerging role of epigenetics in disease. The effect of the chromosomal context and chromatin structure are discussed in relation to gene expression.
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.
Module IV – Mendelian and Non-Mendelian Inheritance in Disease:
This section considers the genetic lesions and the altered function of the encoded proteins in important human diseases. These include a selection of single gene disorders with corresponding genotype / phenotype correlations, and non-mendelian disorders that arise from imprinting defects.
Module V – Genome Evolution and Disease:
This considers the genome as a dynamic structure and begins to consider how the evolutionary pressures on sequence variation and organisation benefits and predisposes to genetic disease. The section considers the role of sequence amplification within the context of the generation of novel gene families and predisposition to genome rearrangements. This is illustrated using the evolution of the sex chromosomes and the MHC as examples.
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
- 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
- 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?
- Cellular heterogeneity in squamous cell carcinoma.