The type VI secretion system (T6SS) is widely used by bacteria to fire diverse effector proteins directly into neighbouring target cells. Many bacterial pathogens employ T6SSs as a potent weapon to deliver antibacterial effector proteins into rival bacterial cells during inter-bacterial competition. Recently, the exciting discovery was made that this ‘anti-bacterial’ T6SS is also a potent anti-fungal weapon, eliciting anti-fungal effectors that are able to kill pathogenic fungal species (1, 2). Our pilot data indicate that T6SS-dependent anti-fungal activity is widespread and mediated by a variety of different anti-fungal effectors, similar to anti-bacterial T6SSs. As bacterial and fungal species frequently co-exist in polymicrobial communities, including the human microbiota and disease-causing infections, we envisage that anti-fungal T6SSs will shape many diverse microbial communities relevant to human health. In the current project, you will join a large well-funded team to take key steps in establishing this exciting new research field by investigating the importance and molecular basis of T6SS mediated anti-fungal activity.
Defining the molecular basis of T6SS mediated anti-fungal activity will be undertaken in Prof Jan Quinn’s laboratory which specialises in fungal stress responses (https://www.ncl.ac.uk/medicalsciences/research/groups/profile/janetquinn.html#background
@NclFungalGroup). Specific techniques include RNA-Seq of T6SS-intoxicated fungal cells to define the genome-wide fungal transcriptional responses elicited by specific effectors, and SGA genetic screens will generate the genetic interaction network for each effector. Such non-biased approaches will direct subsequent molecular and biochemical experiments to define the precise mechanism employed by effectors to kill the fungal cell target.
To explore the physiological relevance of T6SS mediated anti-fungal activity, you will employ a unique ex vivo human intestinal enteroid (“mini guts”) model established in Dr Chris Stuart’s laboratory – an expert in studying human-microbiome interactions (3)
@CJStewart7). Specifically, you’ll determine how anti-fungal T6SSs can influence the nature and outcome of bacterial-fungal co-colonisation of the human gut. This is important as alterations in the intestinal microbiome are associated with human health and many diseases, and roles for the T6SS in the success of both commensal and pathogenic bacteria within gut communities have been recently described.
The Quinn and Stewart labs provide a highly supportive and vibrant training environment, as evidenced by the great track record of previous PhD students. If you are interested in this PhD then you can contact Prof Jan Quinn ([email protected]
) for an informal chat about the project and the research and training opportunities provided.
Benefits of being in the DiMeN DTP:
This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of the-art facilities to deliver high impact research.
We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.
Being funded by the MRC means you can access additional funding for research placements, international training opportunities or internships in science policy, science communication and beyond. See how our current DiMeN students have benefited from this funding here: http://www.dimen.org.uk/overview/student-profiles/flexible-supplement-awards
Further information on the programme can be found on our website: http://www.dimen.org.uk/
1.Trunk KT, Coulthurst SJ, Quinn J. A New Front in Microbial Warfare—Delivery of Antifungal Effectors by the Type VI Secretion System. Journal of Fungi 2019, 5(2), 50.
2. Trunk K, Peltier J, Liu Y-C, Dill BD, Walker L, Gow NAR, Stark MJR, Quinn J, Strahl H, Trost M, Coulthurst SJ. The type VI secretion system deploys antifungal effectors against microbial competitors. Nature Microbiology 2018, 3, 920-931.
3. Stewart CJ, Ajami NJ, et al. Temporal development of the gut microbiome in early childhood from the TEDDY study. Nature 2018, 562, 583-588.