Postgraduate research opportunities

Anti-parasitical drug targeting and validation

Helminth, parasite, drug therapy Cellular Basis of Disease

Number of places

1

Opens

17 February 2020

Deadline

31 July 2020

Duration

36 Months

Eligibility

Biological science degree essential, experience in infectious disease desirable

Project Details

Helminths infect at least a quarter of the world’s population. Leishmaniasis is a protozoan disease responsible for causing different types of diseases and the World Health Organisation estimates that 350 million people are at risk of infection. New drugs for the treatment of leishmaniasis are required as parasite resistance is limiting the number of drugs available for clinical use and multiple-drug treatment regimens appear to be the only way to avoid treatment failure. The United Nations estimates 33% of children from developing countries are stunted in comparison to well-nourished children. Underweight children are at greater risk of dying during childhood and may not achieve their full potential in education and physical performance.  Studies show that children’s growth can be improved by mass treatment with broad-spectrum anthelminthic drugs in populations with a high prevalence of helminth infections. There is very little new drug discovery against helminths (Pharmaprojects database). Small molecule anthelmintics are the primary means of nematode parasite control in animals; however, widespread resistance to currently available drugs means control will be impossible without new compounds. Discovery of new anthelmintic drugs in particular has been a serious challenge due to the difficulty of obtaining and culturing target parasites for high-throughput screens and the lack of genomic techniques to validate potential drug targets in these pathogens.

In this project a novel high throughput screen will be used to identify new drugs for the treatment of leishmaniasis or nematode infection.  Compounds will be screened against different species of Leishmania using the intracellular amastigote stage, IVIS® imaging and luciferase-expressing parasites. A novel assay system will be determined for nematode parasites.  Once active compounds have been identified in vivo efficacy will be determined using a non-invasive route of administration e.g. oral or inhalation. The overall aim is to identify active compounds which can be developed into new drugs.

 

Techniques used:

Histology, ELISA, tissue culture, in vivo biology, FACS, confocal microscopy, 2 photon microscopy, IVIS, parasitology

Funding Details

Applicant will need to self-fund, find sponsorship for tuition and bench fees of £12,000 per annum for duration of studies

Supervisor

Primary Supervisor: Dr Catherine Lawrence

Email: Catherine.lawrence@strath.ac.uk

 

Secondary Supervisor: Dr Chris Carter

Email: k.carter@strath.ac.uk

Further information

Balasegaram M, Ritmeijer K, Lima MA, Burza S, Ortiz Genovese G, Milani B, Gaspani S, Potet J, Chappuis F. Liposomal amphotericin B as a treatment for human leishmaniasis.  Expert Opin Emerg Drugs. 2012 17:493-510 

Geurden T, Chartier C, Fanke J, di Regalbono AF, Traversa D, von Samson-Himmelstjerna G, Demeler J, Vanimisetti HB, Bartram DJ, Denwood MJ.  Anthelmintic resistance to ivermectin and moxidectin in gastrointestinal nematodes of cattle in Europe.  Int J Parasitol Drugs Drug Resist. 20155:163-71.

Alvar J1, Vélez ID, Bern C, Herrero M, Desjeux P, Cano J, Jannin J, den Boer M; WHO Leishmaniasis Control Team. Leishmaniasis worldwide and global estimates of its incidence. PLoS One. 2012 7:e35671.

Alsaadi M1, Italia JL, Mullen AB, Ravi Kumar MN, Candlish AA, Williams RA, Shaw CD, Al Gawhari F, Coombs GH, Wiese M, Thomson AH, Puig-Sellart M, Wallace J, Sharp A, Wheeler L, Warn P, Carter KC.  The efficacy of aerosol treatment with non-ionic surfactant vesicles containing amphotericin B in rodent models of leishmaniasis and pulmonary aspergillosis infection. J Control Release. 2012 160:685-91. 

Contact us

Primary Supervisor: Dr Catherine Lawrence

Email: Catherine.lawrence@strath.ac.uk