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Advanced Topics in Microbiology 2020 – 2021

LESSONS FROM YEAST
Ursula Bond

The yeast Saccharomyces cerevisiae has long been used as a model system for the study of eukaryotic cells. Recent developments have seen this model system used as a powerful experimental tool to understand complex biological processes, particularly those associated with human diseases. The course will explore the experimental approaches and tools that are used to set up a model biological system. With this background information, you will then review some of the seminal papers where studies in yeasts have led to important discoveries into the nature of human diseases such as Huntington’s disease and Parkinson’s disease.

REGULATION OF BACTERIAL GENE EXPRESSION
Charles Dorman

By examining critically the primary literature, this course introduces students to the key breakthrough in the development of current concepts of gene regulation in the prokaryotes. The course will focus on transcription initiation and the factors that modulate it. It will encompass promoter coupling, the global and local effects of DNA supercoiling, the role of the factor for inversion stimulation in transcription and the means by which these regulatory influences are integrated with the stringent response. The relevance of these concepts to bacterial infection will be discussed using specific bacterial pathogens as examples. The impact of genomics technology on current views of global control of gene expression will also be considered. This is a literature-based course and students will have the opportunity to read and discuss the key papers and to assess the experimental evidence on which current understanding of these topics is founded.

CHROMATIN, EPIGENETICS AND DISEASE
Alastair Fleming

It is now accepted that chromatin plays key roles in all aspects of DNA biology including DNA repair, recombination, replication and gene transcription. Arguably one of the hottest topics in biological science today is the area of ‘epigenetics’. Indeed, current research in this area is proving pivotal to our understanding of cancer and stem cell biology. Due to its amenability to genetic manipulation, the yeast Saccharomyces cerevisiae, has served as an excellent model organism for the study of eukaryotic chromatin. In this course we will examine the history of the use of this organism in the study of eukaryotic chromatin. The course will critically cover the primary literature describing the research in yeast that has led to our current understanding of chromatin and epigenetics and its relevance to human disease. We will focus on yeast research in the area of gene transcription in the context of chromatin. The course will be literature-based, and at the end of the course students will have the opportunity to read and discuss current publications at the cutting edge of chromatin research.

SMALL RNA-MEDIATED GENE REGULATION IN GRAM-NEGATIVE BACTERIA
Carsten Kröger

To respond to environmental changes, the gene expression programs in bacteria must be tightly controlled. In addition to gene regulation by transcription factors or DNA topology, small, non-coding RNA molecules have been established as a class of regulatory elements in the bacterial cell. Through the course of this class, we will discuss current knowledge such as the identification, mechanism of action and biological functions of selected small RNAs in Gram-negative bacteria. Guided by selected research articles, we will follow the cellular path of a regulatory sRNA from expression to target interaction and subsequent degradation. The course involves presentation of primary literature by students and discussions on experimental design and interpretation.

RESPIRATORY VIRUSES WITH PANDEMIC POTENTIAL
Kim Roberts

Are there lessons to be learnt about the pandemic potential of respiratory viruses by comparing the virology of coronaviruses and influenza viruses? These two virus families are structurally very different and yet their modes of transmission are similar, and both can produce zoonotic viruses that cause pandemics. In this course we will explore and compare the genomes and replication strategies of coronaviruses and influenza viruses; discuss past and current outbreaks and pandemics; critique experimental evidence for transmission routes; compare pathogenesis; and discuss development of vaccine candidates.

TRENDS IN DRUG DISCOVERY: HOW TO CHANGE THE TIDE ON ANTIBIOTIC RESISTANCE DURING THE COVID-19 ERA
Marta Martins

The rapid emergence of multidrug resistance in bacteria occurring worldwide is jeopardizing the efficacy of available antibiotics, which for decades have saved millions of lives. In addition, the development of new drugs is still declining with pharmaceutical companies curtailing their anti-infective research programs. Antimicrobial resistance is a neglected global crisis that requires urgent attention and action. Appropriate prescription and optimised use of antimicrobials guide the principles of antimicrobial stewardship activities, together with quality diagnosis and treatment, and reduction and prevention of infections. During the current coronavirus disease 2019 (COVID-19) pandemic there are a number of threats that could affect antimicrobial stewardship activities and drive antimicrobial resistance. Furthermore, hospital admissions increase the risk of health-care-associated infections and the transmission of multidrug-resistant organisms, which in turn leads to increased antimicrobial use. In order to tackle these issues, there is the need to re-enforce the discovery of new drugs or to repurpose old ones. This course will discuss the lack of new antimicrobial compounds to fight multidrug resistant infections as well as the problematic use of antibiotics during the COVID-19 pandemic. We will focus on the process of discovery and development of new drugs and the reason why thousands of new molecules never reach the market. Alternative therapeutics: shifting of the current drug discovery paradigm from “finding new drugs” to “combining existing agents”. Some examples of the novel approaches to be discussed include host-directed therapeutics; bacteriophage-based therapies; anti-virulence strategies; development of biofilm inhibitors/disruptors; among others. Using this background information, we will review cutting-edge papers where these approaches are discussed, opening the way to the discovery of new drugs or to the repurpose of old ones. The students will have the opportunity to read and discuss fundamental papers in this area and to critically present their view

Emerging Mechanisms of Host-Microbiome interaction & therapeutic application
Sinéad Corr

An appreciation of the importance of interactions between the human microbiome and the host organism is currently driving research in biology and biomedicine. Microbiome research has gained momentum in recent years, driven by technological advances and improved cost efficiency for analysis. It is widely accepted that the gut microbiome plays a fundamental role in human health and well-being. The constituents of the microbiome have been shown to interact with one another and with the host immune system in ways that influence the development of disease. Models and methods used to evaluate and study the microbiome are critical to developing an accurate understanding of microbiome composition and dynamics and the impact of these for human health. The knowledge gained will enable development of new strategies which leverage applications of the microbiome for new diagnostic techniques and interventional strategies such as personalized medicine. Importantly, as new tools are developed for probing the microbiome and our knowledge grows, a wealth of new questions will arise. This module will take a student-led approach to discuss technological approaches for investigating host-microbiome interactions, as well as recent advances in our understanding of host immunity and microbial influence and arm the student with a broad understanding of the priorities and challenges in microbiome research today. Students will be provided with cutting-edge research articles, offered the opportunity to present the key research findings and critically discuss the implications for the field.