Welcome. If you are interested in signing up for one of my tutorials, please use this site to learn a bit more of what I am offering, and then contact me by email regarding which tutorial would like to sign up for.

I will then respond by email to confirm and provide additional details of the assignment. When possible, full reading list documents will be available here. You are, of course, encouraged to read literature beyond the documents provided here.

Hilary ’21

Salmonella Pathogenesis and Nutritional Immunity

This tutorial will focus on understanding the different steps of a Salmonella infection, both Typhoidal and non-Typhoidal, from both the bacteria’s perspective, and the host’s perspective.

Assignment: 2000-3000 words

Focusing on the bacteria, provide a brief overview of a Salmonella enterica serotype Typhimurium (Salmonella Typhimurium) infection, and a brief overview of a Salmonella enterica serotype Typhi (Salmonella Typhi) infection. Specifically highlight their similarities and differences considering both the enteric and systemic aspects of infection.

Then, focusing on a host, discuss nutritional immunity and how these molecular systems protect a host against infection. How are both Salmonella Typhimurium and Salmonella Typhi able to gain a competitive edge when faced with a host’s nutritional immunity? Besides nutritional immunity, what other immune system responses does the host produce during Salmonella infection, both innate and adaptive (Use the Streptomycin mouse model review for guidance)? Why does the Streptomycin mouse model for Salmonella infection work, and what does this imply about the importance of the innate microbiota and colonization resistance?

Make sure to read about the “Red Queen Hypothesis” in the Nutritional Immunity Review and be prepared to discuss.

You are encouraged to find resources outside of those listed below, and follow your specific interests as the lead you, even if not relating specifically to the prompt above.

Reading list:

Helpful Supplementary material:

A blog post on S. Typhimurium and gut fitness: https://schaechter.asmblog.org/schaechter/2012/03/salmonellas-exclusive-intestinal-restaurant.html

https://science.sciencemag.org/content/366/6468/995.abstract

Michaelmas ’20

Post Translational Modification of Bacterial Weapons: Glycosylation and More.

This tutorial focuses on the post-translational modification of peptide-based toxins produced by bacteria. Your post-translational modification lectures will most likely be focused on eukaryotes, and therefore, this tutorial is best suited for students with a special interest in bacteria, and will serve as a nice perspective from which to compare and contrast prokaryotic and eukaryotic post-translational modification processes

Assignment:  2000-3000 words

Briefly describe and compare N- , O-, C-, and S-linked protein glycosylation mechanisms, and provide a specific example for each.  What role(s) do/does glycosylation play in eukaryotic antimicrobial peptides (AMPs)?  What role(s) do/does glycosylation play for bacterial toxins (bacteriocins)?  Glycosylation of non-ribosomal peptides, and not just proteins, is quite common.  Discuss how Salmonella uses glycosylation to evade host defence mechanisms (Salmochelin), and how some organisms weaponize this system in a similar way to make toxins, known as Class IIb microcins.

Please use any remaining time/words to read and discuss the following:

Other types of microbial warfare PTMs. 

Application of glycosylated protein therapeutics 

Why are glycosylated antimicrobial peptides rare in vertebrates?

Why are there so few known Class IIb microcins?

Glycosylation and SARS-CoV-2 (Spike protein).

Reading list:

Optional reading:

Interbacterial toxins: strategy and diversity

There is a vast breadth of interbacterial toxins discovered to date, with many more being discovered every year. This tutorial will focus on the ecological role of interbacterial toxins, better understanding their diversity, and the strategies bacteria have for choosing when to deploy these costly molecules. Discussion of potential medical or industrial applications will be highly encouraged.

Assignment:  2000-3000 words

First, read through Evolution and Ecology of Bacterial Warfare.  Then, discuss regulation, mechanism of action, spectrum of activity, mode of secretion/release/deployment (ie how does the toxin get out of the producing cell), and depth of diversity of two or three of the following distinct weapon categories (please select T6SS, and at least one bacteriocin group, unless your interests are particularly directed elsewhere):

1. Gram positive bacteriocins (protein toxins)
2. Gram negative bacteriocins (protein toxins)
3. Type 6 Secretion System (T6SS)
4. Small molecules
5. Contact Dependent Inhibition (CDI)
6. Bacteriophage

Despite knowledge of the more physical underpinnings of bacterial weapons, their evolution and ecology remains relatively unknown.  Consider just one of the categories you discuss above and elaborate further on its ecological function and evolutionary pressures.  For motivation, think about and discuss some or all of the following questions:

          Why is regulation of this weapon important?  What potential outcomes would you expect in the absence of regulation (ie constant weapon production/expression)?  Is this primarily an offensive or defensive weapon, or both?  Is it involved in colonisation resistance?  Do all bacteria use this type of weapon, and if not, why?  How much variability in this weapon exists within a species?  How much variability across all bacteria?  How does variability emerge and persist? (For variability questions, if you do not know how much variability exists, form a hypothesis and defend why you think it is true)

If time permits, do some very light reading (e.g. Wikipedia, pop. sci. articles) of the following, for background knowledge on some tutorial discussion points:

• Life cycle and antibiotics of Streptomyces
• Pseudomonas aeruginosa
• Broad spectrum antibiotics (Disruption of normal microbiome)

And finally, consider the image below, representing a theoretical microbial ecological scenario.  We will use this scenario to consider what strategies are most competitive, and how new strategies may emerge and evolve.

Reading list:

Optional/Supplementary reading:

Trinity ’21

No tutorials offered this term