The Bloomsbury Colleges | PhD Studentships | Studentships 2021 | Investigation of microbial community dynamics using in vitro biofilms and in vivo zebrafish infection models
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Investigation of microbial community dynamics using in vitro biofilms and in vivo zebrafish infection models

Principal Supervisor: Dr Brian Ho

Co-Supervisor: Prof Serge Mostowy

Project Description:

The microbiomes found in animals are critical for the wellbeing of their hosts. These microbial communities ensure proper function of several biological processes, ranging from metabolism to immune system development and pathogen resistance. Although numerous studies have investigated the compositional changes that occur in these microbial ecosystems under various disease states, there still exists a major gap in our understanding of how the microbial members of this ecosystem interact with each other, and more importantly, how these interactions scale up to generate stable, health-promoting communities.

The Ho lab has studied these microbial interactions with work focused on the type 6 secretion system (T6SS) and the type 4 secretion system (T4SS), two contact-dependent secretion systems responsible for intercellular antagonism and horizontal gene transfer, respectively. We have found that the specific environmental niche in which the microbial community resides will significantly impact bacterial cell-cell interactions and the bacterial population structure derived from them (Ref 1). However, despite these insights, many details of the bacterial population dynamics in the context of in vivo microbiomes and during host infection remain largely unexplored. Emerging questions include: How are bacteria organized? How do bacterial populations change over time? How do bacterial population structures change as the host responds to infection? Answering these questions will be key to developing new therapies for bacterial diseases in the future.

For this PhD project, we will combine the power of bacterial cell-cell interaction tools (Dr Ho) with zebrafish infection models (Prof Mostowy). Zebrafish infection represents a valuable platform to model human infection. The early embryonic and larval stages of zebrafish are transparent, and development occurs outside the mother (which allows non-invasive high-resolution microscopy). The Mostowy lab pioneered a zebrafish larval model for investigation of bacterial cell-cell interactions (predation, competition), and identified key factors underlying bacterial virulence and host immune evasion (Ref 2).

As part of the Ho and Mostowy labs, microbiology techniques and infection models will enable the investigation of population dynamics in vitro versus in vivo for various combinations of bacteria species, bacterial behaviours (including T6SS, T4SS, host toxicity, host colonization, etc.) and host factors.

Candidate Requirements:

We invite applications from students with good Science undergraduate degrees (first class or upper second), preferably with a Biology component. Previous wet laboratory experience will be valued highly.

Training:

This project will involve a wide range of molecular biology assays (bacterial genetics, genomics, mutagenesis, zebrafish genome engineering), as well as cell biology and microscopy imaging techniques. Additionally, this project will enable the development of computational skills to use simulation/modelling to analyze observed cellular behaviours.

Subject Areas/Keywords

Microbiology, Molecular Biology, Molecular Genetics, Infection, Zebra Fish, Population biology

Key References:

Exploration of T6SS and T4SS dynamics in V. cholerae

Fu Y*, Ho BT*, Mekalanos JJ. Tracking Vibrio cholerae cell-cell interactions during infection reveals bacterial population dynamics within intestinal microenvironments. Cell Host Microbe. 2018 Feb 14;23(2):274-281.e2. doi: 10.1016/j.chom.2017.12.006.

Exploration of bacterial competition in vivo using zebrafish

Ulhuq FR, Gomes MC, Duggan GM, Guo M, Mendonca C, Buchanan G, Chalmers JD, Cao Z, Kneuper H, Murdoch S, Thomson S, Strahl H, Trost M, Mostowy S*, Palmer T*. A membrane-depolarizing toxin substrate of the Staphylococcus aureus type VII secretion system mediates intraspecies competition. Proc Natl Acad Sci U S A. 2020 Aug 25;117(34):20836-20847. doi: 10.1073/pnas.2006110117.

Further details about the project may be obtained from:

Principal Supervisor:

Dr. Brian Ho (b.ho@mail.cryst.bbk.ac.uk, http://www.brianholab.com)

Co-Supervisor:

Dr. Serge Mostowy (serge.mostowy@lshtm.ac.uk, https://themostowylab.org/)

Further information about PhDs at Birkbeck and London School of Hygiene and Tropical Medicine is available from:

Birkbeck college: http://www.bbk.ac.uk/prospective/research

London School of Hygiene and Tropical Medicine: https://www.lshtm.ac.uk/study/courses/research-degrees-and-doctoral-college/doctoral-experience

 

Application forms and details about how to apply are available from:

http://www.bbk.ac.uk/study/2021/phd/programmes/RMPBIOLG/#how-to-apply

Note that you do not need to write your own research proposal. Instead, please state clearly in your application that you are applying for this specific project and use the Supporting Statement in the application to explain what attracted you to the project and why you are a suitable candidate for it.

The successful applicant will be affiliated with the BBSRC-funded London Interdisciplinary Doctoral (LIDo) programme in biosciences (http://lido-dtp.ac.uk/index.html). As part of LIDo the student will undertake two 4-month rotations in the first year (in the labs of the first and second supervisor), will follow the LIDo training programme (including the SysMIC course) and will take part in the annual retreat and other LIDo events, in addition to events organized for Bloomsbury-funded PhD students. However, the student will not be expected to take part in the Professional Internship for PhD Students scheme.

Closing date for applications is: 
1st March, 2021