A balancing act: how hosts control metal availability to their microbiota


   Department of Biosciences

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  Dr K Djoko, Prof J Quinn, Dr N Jakubovucs  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

The human mouth is home to diverse resident microbes and up to 100-200 individual species are commonly detected. These resident microbes play a symbiotic role and contribute to oral health.

Despite repeated exposure to new microorganisms from other environments (eg. via food) and threats of eradication by personal hygiene measures, the composition of the oral microbiota remains relatively stable. The ecological balance of this community is shaped and maintained, at least in part, by saliva and salivary components, which are constantly refreshed (ie. swallowed then replenished). Reduced saliva flow (hyposalivation or dry mouth) is a risk factor for several oral diseases, likely a result of dysbiosis or ecological imbalance within the oral microbiota, which includes disappearance of beneficial microbes, overgrowth of pathogenic microbes, and loss of microbial diversity.

Saliva ensures microbial homeostasis in the mouth via multiple overlapping functions. Salivary (glyco)proteins provide a primary nutritional source for oral microbes. Salivary bicarbonates and phosphates buffer pH to within a friendly, neutral range. Salivary antimicrobial proteins and peptides, such as lysozymes, amylases, and histatins exert direct antimicrobial activity. In addition, research from our group and others has revealed a key role of histatins in buffering copper ions that are potentially toxic to microbes.

PROJECT GOAL

You will study the role of a family of metal-binding salivary peptides in governing the assembly, dynamics, stability, and vulnerability of the oral microbiota. In particular, you will uncover the influence of nutrient metal availability in driving the host-microbiome relationship.

TRAINING

You will be based at the primary supervisor’s laboratory in Durham University and work at co-supervisors’ laboratories at Newcastle University to conduct key components of the study.

Training will be provided in techniques and concepts that span the breadth of biosciences, including microbial genetics, molecular microbiology, microbial physiology, recombinant protein production and characterisation, functional analysis of proteins, and biophysical methods for metal analyses. These will be complemented with key concepts in bioinorganic chemistry. You will also have the opportunity for a 3-month industrial placement of your choice.

To apply:

This project would particularly suit those who are keen to work at the interface of biology and chemistry. If you are interested, you should first contact Dr Karrera Djoko with your CV and a brief cover letter indicating: (i) why you wish to do a PhD; (ii) why you are interested in the project; (iii) what your career goals are beyond the PhD.

HOW TO APPLY

Formal applications should be made by emailing [Email Address Removed] with:

·      a CV (including contact details of at least two academic (or other relevant) referees);

·       a covering letter – clearly stating your first choice project, and optionally 2nd ranked project, as well as including whatever additional information you feel is pertinent to your application; you may wish to indicate, for example, why you are particularly interested in the selected project(s) and at the selected University;

·      copies of your relevant undergraduate degree transcripts and certificates;

·      a copy of your passport (photo page).

A GUIDE TO THE FORMAT REQUIRED FOR THE APPLICATION DOCUMENTS IS AVAILABLE AT https://www.nld-dtp.org.uk/how-apply. Applications not meeting these criteria may be rejected.

In addition to the above items, please email a completed copy of the Additional Details Form (as a Word document) to [Email Address Removed]. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.

The closing date for applications is 10th January 2022 at 5.00pm (UK time).


Funding Notes

Studentships are funded by the Biotechnology and Biological Sciences Research Council (BBSRC) for 4 years. Funding will cover tuition fees at the UK rate only, a Research Training and Support Grant (RTSG) and stipend. We aim to support the most outstanding applicants from outside the UK and are able to offer a limited number of bursaries that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.

References

Role of glutathione in buffering excess intracellular copper in Streptococcus pyogenes. (2020) mBio, e02804-20.
A genetic screen reveals a periplasmic copper chaperone required for nitrite reductase activity in pathogenic Neisseria. (2015) FASEB J, 29(9): 3828-3838.
Pho4 mediates phosphate acquisition in Candida albicans and is vital for stress resistance and metal homeostasis. Molecular Biology of the Cell 2016, 27(17), 2784-2801.
The type VI secretion system deploys antifungal effectors against microbial competitors. Nature Microbiology 2018, 3(8):920-931.
A Critical Role for Extracellular DNA in Dental Plaque Formation. (2017) J Dent Res 96(2):208-216.
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