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.
Dissertation
This should be prepared according to the specific details given by the Faculty Board.
Example Dissertation Titles:
- Immunogenic cell death - a new approach to cancer therapy?
- The origins and evolution of leukaemia
- What is understood of the genetic basis of premature ovarian failure?
- Recent insights into IGF-1 and Cancer.
- The interactions between genetics and epigenetics in colorectal neoplasia.
- Are Psychiatric Disorders Genetic Diseases? The case for Autism.
- Personalised medicine and the future of targeted therapeutics in cancer therapy.
- Testing the Cancer Stem Cell Hypothesis.