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Investigating PDT as targeted herbicidal and antimicrobial agents

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  • Full or part time
    Dr C A Ambler
    Dr N Onkokesung
    Dr GJ Sharples
  • Application Deadline
    No more applications being accepted
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Photodynamic therapies, where light-activation of photosensitisers generate reactive oxygen species (ROS) resulting in cell death, are beginning to show significant clinical efficacy. The ability of ROS to induce cell death is species agnostic, however, application of the underlying technology in non-mammalian species has so far been limited due to the difficulty of generating photoactivatable compounds – antibody, protein or small molecules that can be used in a range of systems including animals, plants, fungi and bacteria.

LightOx, a North-East England-based SME, has developed novel photochemistry that offers a transformational change in the photodynamic therapy (PDT) field through the development of wide range of different small molecular weight, photo-sensitive chemicals. Their size and chemical design facilitates their uptake into both plant and bacterial cells where other photosensitizers cannot penetrate. Initial proof-of-concept work within the collaborative group showed that LightOx photosensitizer compounds can, 1) specifically reduce growth of herbicide resistant black-grass, and 2) act as antimicrobial agents against the Gram-positive bacterium Staphyloccus epidermidis. Although PDT is clinically approved as an anti-infective, the use of PDT is a novel concept in agriculture. In plants, these compounds showed no toxicity in the absence of irradiation. These findings provide convincing evidence that these unique photosensitizers could be employed as a new class of crop protection compounds.

The mechanisms by which PDT kills cells is distinctly different from those in existing herbicides or antibiotics. Herbicide resistance and antibiotic resistance are rising global problems. Thus, the focus of this proof of concept project is to generate evidence on the potential of LightOx’s innovative and targeted technologies to provide new future solutions to address these rising global problems.

HOW TO APPLY

Applications should be made by emailing [Email Address Removed] with a CV (including contact details of at least two academic (or other relevant) referees), and a covering letter – 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 and at the selected University. Applications not meeting these criteria will be rejected.

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

Informal enquiries may be made to [Email Address Removed].

Please note that the closing date for applications is Monday 18th May at 12noon.

Funding Notes

This is a 4 year BBSRC CASE studentship under the Newcastle-Liverpool-Durham DTP. The successful applicant will receive research costs, tuition fees and stipend (£15,009 for 2019-20). The PhD will start in October 2020. Applicants should have, or be expecting to receive, a 2.1 Hons degree (or equivalent) in a relevant subject. EU candidates must have been resident in the UK for 3 years in order to receive full support. Please note, there are 2 stages to the application process.

References

On the antibacterial activity of azacarboxylate ligands: lowered metal ion affinities for some bis-amide derivatives of EDTA do not necessarily mean reduced activity. Chem. Eur. J., 2018, 24: 7137-7148.5.

Exploring the links between peptoid antibacterial activity and toxicity. Med. Chem. Comm., 2017, 8: 886-8969.

Glycosylated nanoparticles as efficient antimicrobial delivery agents. Biomacromolecules, 2016, 17: 2672-2679.

Photoactivated cell-killing involving a low molecular weight, donor-acceptor diphenylacetylene. Chem Sci. 2019 Mar 21;10(17):4673-4683. doi: 10.1039/c9sc00199a. 2018 Impact Factor: 9.556

Fluorescent Retinoic Acid Analogues as Probes for Biochemical and Intracellular Characterization of Retinoid Signaling Pathways. ACS Chem Biol. 2019 Mar 15;14(3):369-377. doi: 10.1021/acschembio.8b00916. 2018 Impact Factor 4.374

Tandem fluorescence and Raman (fluoRaman) characterisation of a novel photosensitiser in colorectal cancer cell line SW480. Analyst. 2018 Dec 3;143(24):6113-6120. doi: 10.1039/c8an01461b. 2018 Impact Factor 4.019

Notch1 recruits RORγ(+) group 3 innate lymphoid cells to orchestrate normal skin repair. Nature Communications. 2016 Apr 21;7:11394. doi: 10.1038/ncomms11394.

Herbicide Metabolism: Crop Selectivity, Bioactivation, Weed Resistance, and Regulation. Weed Science 2019, 67(2), 149-175.

Key role for a glutathione transferase in multiple herbicide resistance in grass weeds. PNAS 2013, 110 (15): 5812-5817. doi: 10.1073/pnas.1221179110

Change in the proteome of the problem weed blackgrass correlating with multiple-herbicide resistance. Plant Journal 2018, 94, 709-720. doi: 10.1111/tpj.13892

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