Assaying the function and antimicrobial activity of slipper limpet hemocyanin

Project Description

Antimicrobial resistance (AMR) is reaching a crisis point, with recent estimates suggesting that by 2050, 10 million people annually will die of from infection by pathogens with AMR. To tackle this crisis both novel antimicrobial therapeutics and better diagnostic tools are needed. Since developing countries will be disproportionately affected by AMR it is also essential that these novel therapeutics can be easily and cheaply produced in bulk.

Hemocyanins are oxygen transport proteins present in the hemolymph (blood) of arthropods and molluscs. In addition to their normal physiological role, molluscan hemocyanins are involved in the host innate immune response. Damage to hemocyanins by either protease treatment or partial denaturation gives rise to phenoloxidase activity, important in the synthesis of the antimicrobial pigment melanin. Proteolysis has also been demonstrated to liberate peptides with antimicrobial activity.

We have recently started investigating the structure and functional properties of a novel hemocyanin from the slipper limpet (Crepidula fornicata) which may be a source of novel antimicrobial peptides; these peptides may represent a new set of tools for countering the growing problem of AMR. Recent preliminary data indicates that the full-length hemocyanin protein, and a protease-treated preparation, shows antibiofilm activity against Staphylococcus aureus.

In this project, we propose to explore this potential antimicrobial and antibiofilm activity further. Using a range of clinically important bacterial and fungal species and in vitro and in vivo (Galleria mellonella) methodologies, we will explore the susceptibility of both planktonic and biofilm (single and mixed species) communities to these compounds. The ability of the compounds to alter microbial pathogenicity and interact synergistically with current antibiotics will also be explored. Experiments will also be performed to fully characterise the functional properties of slipper limpet hemocyanin, quantifying oxygen binding, enzyme activity and fractionating protease-treated preparations to isolate single functional units and active peptides.

This project represents an excellent opportunity for a student to work towards developing novel antibiotics, learning and applying techniques in protein biochemistry, enzyme and ligand binding assays, antimicrobial susceptibility assays, biofilm assays and virulence assays.

How to apply: 

You can apply online – consideration is automatic on applying for a PhD in Biosciences

Please use our online application service at https://www.cardiff.ac.uk/study/postgraduate/research/programmes/programme/biosciences-phd-mphil-md

Please specify that you are applying for this particular project, the supervisor and source of funding.

Information on the application process can be found here

http://www.cardiff.ac.uk/study/postgraduate/applying

Entry requirements-

A 1st or Upper 2nd class UK honours degree or equivalent is usually required.

Suitable for graduates in biological and related sciences, including anatomy, physiology and pathology, aural and oral sciences, biomedical sciences, biology, chemistry, computer science and informatics, forensic science, genetics, medicine, neuroscience, optometry and vision sciences, mathematics and statistics, pharmacology, psychology, sport sciences and zoology.

English Language-

IELTS with an overall score of 6.5 with 5.5 in all subskills, or equivalent. Please see our English Language Requirements guidance for more details.