Defining drug resistance pathways in the malaria parasite
Portugal (PorMSIC) - University of Minho, Braga
Life and Health Sciences Research Institute (ICVS) Universidade do Minho Campus de Gualtar
Maria Isabel Veiga
Maria Isabel Veiga, Pedro Eduardo Ferreira
English, Portuguese
4 weeks
Cities/Months Jan Feb Mar Apr May Jun Jul Augt Sep Oct Nov Dec
No No No No No No Yes No No No No No
Type of Research Project
- Basic science
What is the background of the project?
Artemisinin-based combination therapies (ACTs) have been highly effective over the past decade in treating Plasmodium falciparum infections and reducing the global burden of malaria, a disease that in 2015 alone caused near half million deaths. However, resistance to the core artemisinin component has emerged. Since there are no new drugs commercially available to replace ACTs should they fail globally, there is a compelling need to define the molecular basis of P. falciparum multidrug resistance. Efficiency of ACT drugs can be modulated by mutations in transporter genes which are involved on drug extrusion or in the detoxification pathways. In vitro, ex vivo and molecular epidemiology studies have associated polymorphisms in this transporters with altered parasite susceptibility to multiple ACT partner drugs. However, its cellular and biologic relevance remained constrained by complexities intrinsic to field–based studies, including contributions of polyclonal infections, host immunity and genomic variability.
What is the aim of the project?
The aim is to undergo adefinitive assessment of the role of mutations at the transporter genes, which are prevalent across malaria-endemic countries and assess their molecular role in the drug resistance pathways.
What techniques and methods are used?
The project starts will the culture in vitro of the Malaria parasite. Then it will be analised the transfection based systems and Plasmid design. The student will do polymerase chain reaction (PCR) and electrophoresis. Finally, the last step is to assess drug susceptibility through assays based on parasite grows that is measured by flow cytometry
What is the role of the student?
- The student will observe the practical experiments but will be highly involved in the analysis of the results
- The tasks will be done under supervision
What are the tasks expected to be accomplished by the student?
In 4 weeks the student will not have time to acquire skills enough to handle parasite in vitro culture but it will assist in all experiments. He will learn how to thaw and cryopreserve the malaria parasite, how to maintain them in culture in order to proceed with the experiments. After the student arrival, depending on the status of this project at that time, the student will be able to transfect parasites in order to insert mutations that are prevalent in the field but which importance in drug resistance is still to be validated and perform drug susceptibility tests to this genome edited parasites to understand the impact of the inserted mutations.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
Yes, preliminary readings of research articles and protocols related to the project.
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- The student will prepare a presentation
- The student will prepare a scientific report
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
Concept of working in aseptic conditions and pipetting skills. Some background knowledge on basic molecular techniques such as PCR and plasmid design.
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts:
- Medical students
- Globally prevalent PfMDR1 mutations modulate Plasmodium falciparum susceptibility to artemisinin-based combination therapies M. Isabel Veiga; Satish K. Dhingra; Philipp P. Henrich; Judith Straimer; Nina Gnädig; Anne-Catrin Uhlemann; Rowena E. Martin; Adele M. Lehane; David A. Fidock Nat Commun. 2016; 7: 11553. Published online 2016 May 18. doi: 10.1038/ncomms11553