Dr. Philip J. Shaw, Dr. Chairat Uthaipibull, and Dr. Aiyada Aroonsri, researchers from the Protein-Ligand Engineering and Molecular Biology Laboratory, Medical Molecular Biology Research Unit, were the winners of the DMSc award on medical science research and development for their research on “a ribozyme tool for study of malaria parasite genes”.
The glmS ribozyme is a genetic regulatory element that occurs naturally in many bacterial species. It has the unique property of undergoing self-cleavage of RNA only in the presence of glucosamine, an amino sugar. The BIOTEC team applied this element as a reverse genetic tool in Plasmodium falciparum, the deadliest of human malaria parasites. As proof of concept, the glmS ribozyme sequence was inserted into the dihydrofolate reductase-thymidylate synthase (DHFR-TS) gene, which is the main target of antimalarial drug development efforts in BIOTEC. The BIOTEC team showed that the DHFR-TS gene can be turned off in genetically-modified parasites by glucosamine treatment. Parasites with inactivated DHFR-TS function arrest growth and are significantly more sensitive to antimalarial drugs that are known to target DHFR-TS. Parasites with the same genetic modification were used in a follow-up study to screen antimalarial compounds from the malaria box compound library provided by the Medicines for Malaria Venture (MMV), Switzerland. In this study, the researchers developed a novel screening approach which can identify the in vivo targets of growth inhibitory compounds. Two novel compounds from the MMV library were found to target DHFR-TS. Moreover, in the same study, the glmS ribozyme was shown to work in a similar fashion in Plasmodium berghei, a rodent malaria parasite. The glmS ribozyme tool has been distributed to 21 institutes in 10 countries. Several of these collaborators have successfully applied the glmS ribozyme tool to discover the functions of previously uncharacterized malaria parasite genes essential for host cell remodeling, processing of exported proteins, virulence, hemoglobin catabolism, host cell invasion and nutrient uptake. These new findings have been published in high-profile journals, which have garnered over 100 citations from other scientific reports. The knowledge gained from research using the glmS ribozyme tool will be very useful for developing new antimalarial drugs, which are urgently needed to counter the threat posed by malaria parasites resistant to currently used drugs.
The 25th Annual Medical Sciences Conference was held by the Department of Medical Sciences (DMSc), at IMPACT Forum, Muang Thong Thani on 22-24 March 2017. There are 3 types of awards: awards for medical science research and development; awards on medical science book/textbook; and awards on the improvement in service quality of medical science.
Posted on March 27, 2017