Advanced Topics in Microbiology 2022 – 2023
LESSONS FROM YEAST: CHROMATIN, EPIGENETICS AND DISEASE
Dr. Alastair Fleming
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 first part of this course will explore the experimental approaches offered by yeast as a model biological system. With this background information, you will review how many of the fundamental chromatin-mediated cellular processes were first identified in yeast and were then found to exist in human cells. Finally, we will discuss how using yeast as a model organism has offered insight into when chromatin-mediated processes become aberrant and the relevance of this failure of function to cellular aging and cancer.
Topics discussed in first 7 lectures:
1: Yeast as a Model Organism
2: The Yeast Deletion Library: Looking for Phenotypes
3: A brief history of chromatin research: from obscurity to the cutting edge
4 & 5: Early studies in yeast which first demonstrated chromatin regulates transcription
6: Chromatin and aging
7: Chromatin and cancer
Sessions 8, 9 and 10 will involve class discussion of topical papers (to be selected).
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. Throughout the course of this class, we will discuss current knowledge such as the identification, mechanism of action and biological functions of selected small RNAs and their RNA-binding proteins 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 in-depth reading of primary literature as a group and discussions on experimental design and interpretation.
Transmission of respiratory viruses
Kim Roberts
There has been considerable debate about the routes of transmission of respiratory viruses, such as influenza A and SARS-CoV-2. During the COVID19 pandemic, many people have questioned the evidence, definitions, and biological relevance of fomite vs respiratory droplet vs airborne transmission, creating a new body of work investigating this topic.
In this course we will explore and compare the range of different types of viruses that can cause respiratory infection, from common cold-causing adenovirus and rhinovirus to viruses with pandemic potential like SARS-CoV-2 and Nipha virus. We will discuss the biological properties of viruses that impact the efficiency of their transmission. For example, using SARS-CoV-2 and influenza A variants we will explore how mutations in viral receptor binding proteins increase (or decrease) infection and transmission efficiency. We will also explore host adaptations that enable viruses to cause zoonotic outbreaks. We will examine environmental factors that can affect transmission efficiency, such as temperature, humidity and ventilation. Finally, we will discuss the evidence for/against different non-pharmaceutical interventions that are used to reduce respiratory virus transmission. Throughout the course we will work together to identify general principles that could help prepare society for future respiratory virus pandemics.
The course will be divided into five 2-hour (2x 45 minutes with a break in the middle) classes:
- Viruses that cause respiratory infections
- Routes of respiratory virus transmission and their impact on disease
- Viral adaptations that affect transmission and pandemic potential
- Environmental factors that affect transmission
- Non-pharmaceutical interventions to reduce respiratory virus transmission
Each class will be comprised of a mixture of lecture material, recommended multimedia resources, as well as critique and discussion of review and primary papers. All students are expected to engage with the material provided ahead of the classes and to participate in the class discussions.
“THE SILENT PANDEMIC: TACKLING ANTIBIOTIC RESISTANCE ON ESKAPE PATHOGENS BY EXPLORING NEW TRENDS IN DRUG DISCOVERY AND THERAPEUTICS”
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 “silent pandemic” constituting 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. However, there are several threats that can 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 2017, the WHO published a list of pathogens for which new antimicrobial development is urgently needed. Within this list, ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens were designated “priority status”. This highlights the urgency in the development and discovery of new drugs or the repurpose of ‘old ones’. This course will discuss the lack of new antimicrobial compounds to treat multidrug resistant infections (namely the ones caused by ESKAPE pathogens), as well as the problematic (mis)use of antibiotics. 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. We will also discuss the use of potential alternative therapeutics that are focused on shifting the current drug discovery paradigm from “finding new drugs” to “combining existing agents”. Some examples of the approaches to be discussed can 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 as well as to work with their peers in critically presenting their view about antimicrobial resistance. Group work will be focused on potential solutions to tackle this public health issue and discover/design a new antimicrobial.
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 the opportunity to identify and examine cutting-edge research articles, to present the key research findings and critically discuss the implications for the field.
AN INTRODUCTION TO EVOLUTIONARY MICROBIOLOGY
Siobhán O'Brien
Microbes show a remarkable ability to rapidly adapt to harsh and changing environments. Such rapid evolution can have direct consequences for our health and wellbeing. Antimicrobial resistance, vaccine escape and the switch from acute to chronic infection are all driven by the evolution and spread of adapted strains. Our understanding of microbial evolution has been transformed by real-time experimental evolution in the laboratory. This “living fossil record” allows us to examine the drivers of evolutionary change in pathogens, identify novel genomic mutations over evolutionary timescales and quantify the “fitness advantages” conferred by them.
This course will introduce you to the concept of microbial evolution by way of examining and discussing the most recent and cutting-edge literature in the field. You will learn about what drives the rate and likelihood of evolutionary change as well as how we might leverage or “hijack” evolution to minimise the negative effect a pathogen may have on their host. We will take a closer look at one of the longest running evolution experiments in history – twelve flasks of E. coli evolving for over 50,000 bacterial generations by Rich Lenski’s lab at Michigan State University. Expect fitness conflicts, trade-offs, bacterial warfare and invasions.
ARMS RACE IN MICROBIOLOGY: COEVOLUTION OF BACTERIAL DEFENCE AND PHAGE COUNTER-DEFENCE MECHANISMS
Anna Ershova
Learning aims: To expand student knowledge of bacteria-phage coevolution in microbial communities.
Module content:
This module will include 10 lectures on bacterial defence and phage counter-defence mechanisms and their effects on community structure and evolution. Many different systems protect bacteria from foreign DNA invasion. Bacteriophages developed various mechanisms to avoid bacterial defence systems. Together, these mechanisms shape bacterial communities and gene flow in the population.
Learning outcomes:
- To understand the diversity of bacterial and bacteriophage defence mechanisms
- To understand the effect of bacterial defence and bacteriophage counter-defence mechanisms on the evolution of microbial communities
CLONAL EVOLUTION: INSIGHTS FROM MICROBES, CANCER, AND INFECTIOUS DISEASE
Máire Ní Leathlobhair
Clonal or asexual reproduction stands as one of the most ancient and widespread mechanisms of cellular propagation. Its scope extends from unicellular microorganisms like viruses, bacteria, and parasites to complex multicellular eukaryotes, including animals and even cancers. This advanced topic delves into the fundamental evolutionary principles and processes that underlie clonal evolution across diverse organisms. By leveraging this evolutionary framework, we can link the fields of microbiology, cancer biology, and infectious disease.
Cancers arise via somatic clonal evolution and a large part of this course will explore the dynamics of cancer cell populations. We will see how experimental microbial systems can be used to understand these complex dynamics. We will consider the consequences of clonality on population and genome structure over long versus short time scales. Finally, we will look at rare clonally transmissible cancers that have the innate ability to be communicable and pass horizontally from host to host, behaving more like infectious unicellular parasites than conventional cancer cells.
Throughout this module, we'll engage in a dynamic exploration of classical papers and cutting-edge research on clonal evolution. Our discussions will be motivated by the presentation of recent papers to peers, promoting a collaborative environment, insightful conversations and a nuanced understanding of this subject.