The course is organised into 5 modules from which you select 4, ensuring that you acquire the necessary breadth of background in the subject. Each module is made up of ~24 lectures. The modules aim to cover the range of genetics from cellular to organism level and will show how the latest developments (in areas such as sequencing technologies and genome assembly, functional and computational biology) are being applied to the problems of how genes in different species are organised, expressed and interact, to give the final phenotype.
Michaelmas Term (2/2) – no options:
Module 1: Genomes
Module 2: Early Development & Patterning: Genetic & Cellular Mechanisms
Lent Term (2/3) – you select 2 modules out of:
Module 3: Genetics of Health & Disease
Module 4: Evolutionary Genetics & Adaptation
Module 5: Mathematical Genetics
Module 1 : Genomes (MT)
This module will explore how genomes are organised and maintained. We will start by exploring the control mechanisms that promote correct cell cycle progression and the accurate segregation of genes and chromosomes into daughter cells at cell division, centred on key cell cycle protein kinases, phosphatases and checkpoints. The module will examine how genomes are sequenced, the sequence assembled and how sequence-based technologies, like Hi-C, reveal organisation at the chromosome level. The make-up of genomes will be considered from genes and their regulatory elements, to the importance of genetic variation and the non-coding genome and repeat DNAs. We will introduce the genomics approaches that underpin the functional analysis of genomes, including technologies for measuring gene expression, transcriptional activity and chromatin states. The final lecture block will focus on the organisation of DNA and the proteins associated with it. The physicochemical regulation of chromatin structure and the contribution of liquid-liquid phase separation to genome and nuclear organisation will be examined. The origin of the eukaryotic nucleosome will be considered by examining the solutions arrived at in prokaryotes and archaea.
Module 2 : Early Development & Patterning: Genetic & Cellular Mechanisms (MT)
This module will cover how the early embryo develops from a fertilised egg to form the body plan. By comparing the body plan formation across phyla, you will be introduced to both conserved and divergent mechanisms of development.
You will learn about the key principles of embryonic development, taking examples from a range of early developmental events, such as cell fate determination, germline development, gastrulation, segmentation, and somitogenesis, in both invertebrate and vertebrate systems.
The aim is to use examples from a broad range of experimental systems that provide a detailed understanding of cell and molecular biology in action. This includes the intersection of gene regulatory networks and signalling in pattern formation, the role of cell polarity in cell fate determination and morphogenesis, how the acto-myosin cytoskeleton drives tissue morphogenesis and the role of mechanical forces in coordinating multi-tissue morphogenesis. It will enable students to understand how emergent properties play out during embryogenesis: from the genetic control of cellular behaviours to the ways cellular collectives result in the shaping and folding of tissues. A comparative approach will highlight these essential principles of developmental biology.
Module 3 : Genetics of Health & Disease (LT)
This module will be human-centric and, while it will look at some specific diseases, it will focus more on genetic approaches to understanding disease mechanisms and developing therapies, rather than on shallower coverage of an extensive list of diseases. The module will look at human mutation, and the genetic approaches to both monogenic and multigenic diseases. Monogenic diseases include the growing number of rare diseases emerging from genome sequencing in the clinic. While individually rare, they are collectively common, and can be informative about the basic biology and disease mechanisms of more common diseases. Multigenic diseases include many common conditions with a genetic component and we will address approaches to identifying the causative genes, such as genome-wide association studies, and how they help us to understand the disease. Implications for personalised medicine are also discussed. We will examine the genetics of infectious disease agents, including microbial genomics and phylogenetics, applied microbial genomics in clinical and public health, phylogeographic and phylodynamic models, pathogen epidemiology and antigenic evolution at scale, ancient DNA in study of pathogen evolution and transmission and sequencing approaches to understand microbiome diversity and function. This module will also look at diseases for which genetic approaches have revealed much about their mechanisms, and potentially also therapies – neurodegenerative diseases (such as Parkinson’s or Alzheimer’s), mitochondrial disorders, genomic imprinting disorders and cancer.
Modern evolutionary theory has its roots in the union of Mendelian genetics with Darwin’s theory of evolution, two of the great unifying themes of biology. This course will consider the process of evolution from a genetic perspective, exploring the central topics of natural selection, adaptation and genetic drift, and combining a variety of empirical and theoretical approaches. Alongside this, the course will explore how genomes themselves are shaped by selection, drift and their evolutionary history. The first half of the module will explore the genetic basis of adaptation. Do we expect evolutionary change to involve few or many genes, and how might we go about identifying the genes underlying a particular trait? What kinds of genes control evolutionary changes in morphological traits? We look at the genes underlying convergent evolution as a way of understanding the predictability of evolutionary change. Genomic data contain a wealth of information about the history of populations and natural selection, and population genetics provides a framework to reconstruct these processes.
The second half of the module will look at the evolution of genomes and conflict within genomes. We will begin by examining the evolution of key features of genomes – sex chromosomes, introns, repetitive DNA, gene expression and mutation rates. We will finish by considering one of the conundrums of evolutionary biology – why some species reproduce sexually – from a theoretical and empirical perspective.
Module 5 : Mathematical Genetics (LT)
The aim of this module will be to give students a thorough grounding in mathematical approaches to the study of genetics. Emphasis will be placed on fundamental principles, equipping students with a deeper understanding of the various roles of mathematics in the field, and the ability to understand, and even develop, the next generation of tools. The material covered will include the nature and uses of mathematical models, including latent variable models, and statistical methods of inference. The course will also cover topics relevant to particular areas of genetics, including evolutionary, developmental, and biophysical genetics, as well as other subfields that link genotype to phenotype. These topics will include mathematical population genetics (including the coalescent approach, which underpins inferences from genomic sequence data); quantitative genetics (the inheritance, architecture and evolution of complex and continuously-varying traits); dimensionality reduction approaches, which are essential to understanding large data sets (e.g. single-cell data), and dynamical systems modelling of gene regulatory networks.
