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Advanced Topics in Microbiology 2018 – 2019

LESSONS FROM YEASTS

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. This course will explore the experimental approaches used to set up a model biological system as well discuss project “Yeast 2.0”, which aims to create an “artificial microorganism” using synthetic chromosomes. With this background information, we will thenreview 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 diseaseAdditionally, we will discuss how yeasts such as Saccharomyces cerevisiae and Saccharomyces pastorianus have evolved into ideal fermentative microorganisms for use in brewing, baking and wine-making industries.

REGULATION OF BACTERIAL GENE EXPRESSION

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

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.

THE MOLECULAR BASIS OF IMMUNE EVASION BY STAPHYLOCOCCUS AUREUS

This course will deal with the strategies used by S. aureus to twart the human immune system with particular focus on the arsenal of molecules produced by the bacterium to inhibit phagocytosis and neutrophil-mediated killing. The topic will be introduced with two lectures and the remainder of the course will involve student-led discussion sessions. Primary research articles will form the basis of class discussion of the experimental evidence on which our understanding of staphylococcal immune evasion is based. Elements of scientific research practices will be incorporated into the sessions to encourage students to develop skills in experimental design, analysis and interpretation.

DRUG REPURPOSING TO MEET THE CHALLENGE OF ANTIMICROBIAL RESISTANCE - “A BATTLE OF THE TITANS”

Antimicrobial drug resistance (AMR) is an urgent global health problem. The rapid emergence of AMR in bacteria occurring worldwide is jeopardizing the efficacy of available antibiotics, which for decades have saved millions of lives. New antimicrobial drug development is increasingly viewed as a priority by National and International bodies. Pharmaceutical companies are curtailing their anti-infective research programs. Adding to this, there are relatively few agents in developmental pipelines and a paucity of identified microbiological targets that can be exploited for drug development. In order to tackle this issue there is the need to re-enforce the repurpose of existing drugs that were set aside through the years due to the enormous availability of antibiotics. This course will discuss the problematic lack of new antimicrobial compounds to fight multidrug resistant infections. Two main areas will be the subjects of discussion: 1. Drug repurposing: the process of repurpose the use of “old drugs” and the reason why thousands of these molecules were left behind and aren’t able to reach the market; 2. Alternative therapeutics: shifting of the current drug discovery paradigm from “finding new drugs” to “using existing ones” or “combining existing agents”. Some examples of the novel approaches to be discussed will 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 repurposing of existing drugs. The students will have the opportunity to read and discuss fundamental papers in this area and to critically present their view on this subject.

SMALL RNA-MEDIATED GENE REGULATION IN GRAM-NEGATIVE BACTERIA

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 the current knowledge about identification, mechanisms and 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 the students and discussion about experimental design and interpretation

VIRAL PATHOGENESIS

How do viruses cause disease? Why are some strains of a virus more virulent and cause more severe disease than other strains? How do viruses inhibit the innate immune response and what is a virus induced “cytokine storm”? What makes some people more susceptible (or resistant) to viral infection? Viruses are a diverse group of molecular machines and so there are many answers to these questions. In this course we will discuss a range of virus examples to explore viral pathogenesis and consider some of the experimental techniques being used to dissect this fascinating field of study. This course is delivered through interactive lectures and critical, group discussions of primary research papers.

CELL BIOLOGY OF ‘SELECT AGENTS’

In the early 2000s, the US Federal Select Agent Program (FSAP) was established in the light of an increasing risk of bioterrorist attacks. Encompassing biological agents and toxins with the potential to pose a severe threat to public health and safety, the current ‘select agent’ list contains approximately 70 agents and/or toxins. While threats such as smallpox, anthrax and bubonic plague are well known, this course will focus on 3 lesser known bacterial agents on the list, namely those responsible for the diseases Brucellosis (Brucella spp.), Q Fever (Coxiella burnetii) and Tularaemia (Francisella tularensis). The module will take a student-led approach to explore the history of these bacterial pathogens, aspects of pathogenesis and disease that establish these organisms as select agents, alongside the Select Agent Program itself. Students will be provided with primary research articles and scientific reviews and, in a group format, present and discuss these with the class.