Spore formation in model and pathogenic bacteria
Primary Supervisor: Associate Professor Christopher Rodrigues, School of Life Sciences
Secondary supervisor: Associate Professor Meera Unnikrishan & Associate Professor Munehiro Asally
PhD project title: Spore formation in model and pathogenic bacteria
University of Registration: University of Warwick
Spore development or sporulation is one of the earliest forms of cellular development on Earth and functions as a survival strategy against starvation. Its primordial nature has allowed it to serve as an excellent model system for understanding broadly relevant molecular aspects of cellular developmental. Furthermore, the various morphogenetic processes that underlie sporulation have made it a sophisticated model for understanding molecular mechanisms in bacterial biology. Importantly, spore resist stresses including: antibiotics, detergents, UV radiation and high temperatures. Their dormant nature and resistance to these stressors allows them to persist in the environment for extended periods of time and when nutrients become available, spores emerge from dormancy to generate growing populations of bacteria. For this reason, spores are considered the vehicle of new and recurring infections in humans, animals and insects, and can contaminate food sources.
Given the lack of antibiotics specifically targeting sporulation, the prevalence of spore-forming pathogens in hospitals worldwide and existence of spore-forming pathogens that cause disease in pollinator insects (honey bees), understanding sporulation is important as a mean to provide a platform for translational opportunities controlling spore-forming bacteria.
Importantly, although bacterial sporulation is restricted to a single phylum, there are likely to be many variations at a mechanistic level, particularly if we consider how spore-forming bacteria grow and sporulate inside hosts and the likely molecular mechanisms that tie host physiology to growth and sporulation. Thus, it is important to investigate sporulation in understudied bacteria and in the host context.
Despite decades of research, important questions regarding spore molecular biology and physiology remain to be solved and are the focus of the Rodrigues Laboratory (Rodrigues Lab). PhD projects exploring the following questions, using the human pathogen Clostridioides difficile, the honey-bee pathogen Paenibacillus larvae or model organism Bacillus subtilis, in collaboration with other laboratories (Munehiro Asally and Meera Unnikrishnan, depending on the project), are available for consideration by enthusiastic students.
- How do conserved sporulation genes function during spore development?
Building on our existing work, we are particularly interested in investigating the assembly of the spore envelope with a strong focus on the spore cell wall and its relationship to other processes during development, in Bacillus subtilis and Clostridioides difficile.
Recommended articles include:
- How do spore-forming pathogens grow, sporulate and cause disease in their hosts?
We are particularly interested in the sporulation program of Paenibacillus larvae, which causes American foulbrood disease in honey bee larvae. Our goal is to develop a new model and tools for studying sporulation directly in a host setting.
- What are the metabolic circuits that control spore dormancy?
Based on previous work and unpublished results, we are interested in the function of a poorly characterized secretion system and how it contributes to spore metabolism.
Recommended articles include:
Trends in Microbiology_Rodrigues
BBSRC Strategic Research Priority: Understanding the Rules of Life:Microbiology
Techniques that will be undertaken during the project:
- Live cell fluorescence microscopy
- Quantitative image analysis (e.g. ratiometric imaging with biosensors)
- Microbial cell cultivation and transformation
- Transposon-sequencing / Tradis
- Molecular biology & genetic approaches (PCR, cloning, isothermal assembly, site-directed mutagenesis)
Contact: Dr Christopher Rodrigues, University of Warwick