Module Identifier BS32420  
Academic Year 2001/2002  
Co-ordinator Dr Paul Kenton  
Semester Semester 2  
Other staff Dr Gareth Griffith, Dr Richard Kemp, Dr Rodney Turner  
Pre-Requisite BS10510  
Course delivery Lecture   30 Hours  
  Workshop   2 Hours 2 x 3 hours  
Assessment Practical exercise   Continuous assessment of practicals/seminars   15%  
  Exam   3 Hours One 3-hour theory paper   70%  
  Exam   3 Hours One 1-hour multiple choice paper    
  Resit assessment   3 Hours One 3-hour theory paper (plus resubmission of failed coursework or an alternative)   100%  

Aims and objectives

The mechanisms by which individual cells regulate expression of a particular subset of the entire genome is of fundamental importance in understanding development. In this module we shall examine how the ultimate expression of the genome, the proteome, is controlled and how this is achieved in several important developmental processes.


Gene Expression: The main section of the module will examine the control of gene expression. We shall start by examining the structure of eukaryotic genes including exons and introns, repetitive sequences, gene clusters, and the relevance of copy number. rRNA and tRNA genes will also be examined. The first point during expression at which a significant level of control is exerted is transcription. Here the effects of chromatin structure and DNA packaging on transcriptional activity will be discussed and the structure of RNA polymerase recognition sites and the assembly of the transcription initiation complex will be examined. We shall then consider regulation by transcription factors discussing types of transcription factors, their activation, and mechanisms by which they interact with DNA. We shall also examine promoters and cis elements. Other aspects of expression regulation (DNA methylation, imprinting and silencing) will also be introduced. We shall also take a close look at aspects of nuclear structure that are relevant to regulation of expression.
The next regulatory stage occurs when pre-mRNA undergoes a substantial degree of processing. We shall concentrate on aspects of mRNA processing such as the spliceosome, exon/intron boundary recognition and alternate splicing, and capping and poly-adenylation. We shall also examine other splicing mechanisms and rRNA and tRNA splicing. Further control of expression occurs at the level of transcript availability. In this topic aspects such as mRNA localisation and half- life will be discussed. Translation can also be regulated by the activation of signalling pathways and by modifications to key components such as initiation factors. Following synthesis, a polypeptide may undergo further post-translational processing e.g. proteolysis or addition of non-protein moieties such as carbohydrates. Many proteins contain sequences that target them to specific subcellular locations. The final act in the regulation of gene expression is the control over the life-span of proteins. Here we shall examine the mechanisms by which proteins are removed and how this can be controlled.
Special Topics: In this section we shall examine the molecular biology of three important developmental processes. Programmed Cell Death (PCD) is an important process in development and homeostasis. We shall discuss initiation and signalling in PCD, `anti-` and `pro-PCD? genes, and transcriptional activation of PCD. In Oncogenesis we shall examine the molecular processes behind cancer, examining the relationship between oncogenes and proto-oncogenes, the role of chromosomal abnormalities in tumour etiology and the mechanisms by which human tumour viruses cause cancer. Generation of immunological diversity will discuss the mechanisms by which diversity in B and T cell receptor specificity is generated, as well as the molecular biological aspects of immune cell ontogeny. In Genetics of Asexual Reproduction in Fungi the way in which a cascade of transcriptional activators regulates aspects of conidiation in Aspergillus nidulans will be examined. The roles of other genes in this aspect of fungal reproduction will also be discussed.

Learning outcomes

On completion of the module the student
? should have a thorough understanding of the multiple control points at which gene expression can be regulated
? will have studied three examples of crucial developmental processes that rely on the regulation of gene expression
? should be able to interpret other developmental processes in the light of these fundamental concepts.

Reading Lists

** Recommended Text
Lewin, B. (1999) Gene VII. Oxford University Press.
Alberts, B. Bray,D., Lewis, J., Raff, m., Roebrts, K. & Watson, J.D.. (1994) Moelcular Biology. Oxford University Press.