Host colonisation in mosquito-associated bacteria

Given the rise of insecticide resistance and the invasion of vectors into new areas in the course of climate change and urbanisation; new, alternative approaches to vector control are urgently needed. Ideal control measures can be used in conjunction with already existing ones to avoid reliance on one single method, which renders the system inflexible and control failure has dramatic consequences until a replacement is found.

An attractive approach is the use of mosquito-associated bacteria as delivery vehicles for toxins or other modifying traits; which can lead to death of the mosquito, blocking of arboviral infection, or reducing the mosquito lifespan. However, whilst a large body of work is ongoing to find the delivered toxins or other genetic manipulation methods; we still have very limited understanding of the bacteria inhabiting the midgut; which however are one of the two essential components, i.e. the delivery vehicle of the trait of interest.

This PhD proposal will be embedded in the closely interlinked teams of Grant Hughes (GLH; mosquito microbiomes) and Eva Heinz (EH; microbial genomics), and address one of the key features in any host-pathogen relationship: the bacterial cell surface, and what distinguishes bacterial symbionts from other bacteria that are taken up by the mosquito, but do not manage to form a stable relationship. As midgut symbionts experience a rapid host – environment transition due to the short life span of their hosts, as opposed to the main model organisms (human, mouse), this project also aims to model how much more efficient certain adhesion factors make establishment as symbiont, and to what extent the interim time in the environment influences this, as this has an impact to colonisation in densely vs. sparsely mosquito-inhabited areas.

This project will be placed in the collaborative work between EH and GLH, which includes a five-year funded BBSRC-NSF grant, where this position will use mosquito midgut-derived whole-genome sequence data generated in the course of this larger project, and focus on the diversity and evolution of surface protein families as well as the relevance of cell surface polysaccharides in the ability of bacteria to colonize the mosquito host.

Where does the project lie on the Translational Pathway?

T1 (Basic Research – T2 (Human/Clinical Research)

Expected Outputs

The project will produce high quality REF returnable 3*/4* publications and will provide essential data for translational follow-up work on using microbes to control arboviral vectors. Previous and current PhD students from EH have all published one or several high-quality first-author papers, including Molecular Microbiology, PLoS Pathogens and Nucleic Acids Research, and have all moved to postdoctoral positions or are working as programmer in industry. Recent work from EH and GLH on mosquito microbiomes has resulted in high-quality publications in the ISME Journal, PLoS Pathogens and PLoS NTD. The project will have the unique opportunity to access large-scale sequence data from mosquito-derived symbionts which will be generated in the course of a shared 5-year BBSRC/NSF-funded project by EH, GLH and Dr. Kerri Coon (USA). The student will furthermore be embedded in the larger collaborative network around EH and GH, which includes Dr. Coon (group leader at University of Wisconsin-Madison, USA) and Prof. Corander (Wellcome Sanger Institute), and a wide range of collaborations around microbial genomics (EH) and mosquito microbiomes (GLH). This is a key strategic area for LSTM as evidenced by the recent appointment of EH and GLH who were recruited from the prestigious Wellcome Sanger Institute and the University of Texas Medical Branch, respectively.

Training Opportunities

Training will be provided in bioinformatics (molecular evolution, comparative genomics, host-pathogen interaction, protein family evolution), statistics, evolutionary models (EH); insectary work and molecular microbiology (GLH). The student will furthermore work with collaborators at the Wellcome Sanger Institute, Lancaster University, and in the US, and be embedded in the already closely collaborating network between the supervisory team and further collaborators world-wide.

Skills Required

The student should be interested in bioinformatics, in particular genome evolution, host-pathogen interactions and co-evolution.

Key Publications associated with this project

Kozlova et al. 2020 ISME Journal; Microbial interactions in the mosquito gut determine Serratia colonization and blood-feeding propensity.

Horesh et al. 2020 Nucleic Acids Research; Type II and type IV toxin–antitoxin systems show different evolutionary patterns in the global Klebsiella pneumoniae population

Hegde et al. 2019 PLoS NTD; CRISPR/Cas9-mediated gene deletion of the ompA gene in symbiotic Cedecea neteri impairs biofilm formation and reduces gut colonization of Aedes aegypti mosquitoes

Heinz et al. 2016 Genome Biology and Evolution; Conserved features in the structure, mechanism, and biogenesis of the inverse autotransporter protein family

Heinz et al. 2015 Genome Biology and Evolution; Evolution of the translocation and assembly module (TAM)

Deadline: Thursday 11th February 2021; 12:00 noon GMT

Further details on the MRC/DTP and CASE programmes and application guidance and process can be found here