Introduction of a new drug discovery workflow using a nanoluciferase malaria parasite
Malaria is a deadly disease that affected over 240 million people in 2020, an increase over progress in previous years. Despite advances in malariology, the challenge of finding the right drugs to treat the illness is complex.
During this hourlong webinar, drug discovery experts Dr James Duffy (Medicines for Malaria Ventures (MMV)), Dr Koen Dechering (TropIQ) and Martijn Timmerman (Pivot Park Screening Center (PPSC)) will share:
- perspectives and strategies in antimalaria drug discovery
- the biology of the malaria models
- small molecule tactics and technical assay development
- a novel transgenic malaria reporter strain with excellent performance in high-throughput screening
- screening and hit generation of active compounds against the blood stage of the Plasmodium falciparum parasite
- triage of large compound libraries screening
About the presenters:
Dr James Duffy, Director of Drug Discovery, Medicines for Malaria Venture (MMV)
James Duffy is a Director of Drug Discovery at Medicines for Malaria Venture (MMV) with 21 years’ experience working in drug discovery. He has a special interest in malaria and other infectious diseases that disproportionately affect vulnerable populations. Working at MMV, he is part of the global efforts to reduce the burden of malaria in disease-endemic countries by discovering, developing and delivering new, effective and affordable antimalarial drugs.
James’ current role is to provide drug discovery expertise and strategic leadership to multidisciplinary collaborations with academic, biotechnology and pharmaceutical partners. He obtained his PhD from the University of Sussex (Brighton, UK) and prior to MMV worked at BioFocus (Cambridge, UK) where he was a co-inventor of the FDA approved HDAC inhibitor Belinostat.
Dr Koen Dechering, CEO, TropIQ Health Sciences
Koen Dechering pioneered the study of gene regulation during sexual development of malaria parasites and received his PhD in 1998. He then joined the pharmaceutical industry and worked with Organon, Schering-Plough and Merck Sharp & Dohme to develop novel drugs for the treatment of endocrinological disorders. He combined his industrial career with an assistant professorship in applied biology at the Radboud University in the Netherlands. In 2011, Koen founded TropIQ Health Sciences with the aim of accelerating the development of novel therapies against tropical infectious diseases. The company develops innovative technologies for the assessment of novel therapeutics. In addition, it uses its technology platform to drive a proprietary drug discovery program centered around molecules that target pathogens or their insect vectors.
Martijn Timmerman, scientist, Pivot Park Screening Centre
Martijn Timmerman is a scientist at Pivot Park Screening Centre with many years of experience in the validation and automation of high-throughput assays. He joined PPSC almost 10 years ago and performed numerous screening campaigns.
Prior to PPSC, he worked at TropIQ Health Sciences where he learned the basics of malaria parasitology. Martijn started his career at Organon/Schering-Plough/Merck in the molecular pharmacology department. Here he was already developing and validating all kinds of assays suitable for screening purposes.
Part 1: perspective on antimalarials and overall strategy
James Duffy will open the webinar by explaining that, despite advances in our understanding of the underlying molecular basis of malaria and there being several new combination therapies in clinical development, new, affordable and safe malaria medicines are urgently required to:
- overcome increasing resistance against artemisinin-based combination treatments to treat vulnerable populations
- interrupt the parasite life cycle by blocking transmission to the vectors
- prevent infection and target parasite species that remain dormant in the liver
part 2: Introduction to biology of malaria models
Secondly, Koen Dechering will introduce a novel reporter parasite that was generated by integration of a nanoluciferase expression cassette into the parasite’s genome and demonstrate the reporter’s sensitivity and reproducibility in high throughput screening formats.
Furthermore, he will:
- discuss pros and cons of phenotypic versus target-based screening
- the life cycle of the malaria parasite and discuss the challenges in malaria drug discovery
Part 3: Small molecule tactics and technical assay development on malaria models
Thirdly, Martijn Timmerman will discuss:
- miniaturization and optimization of a 1536-well screening assay to screen the blood-stage of P. falciparum
- the importance of triaging after the screening of a 140,000-compound library
Part 4: Hit prioritization discussion
Lastly, James Duffy will present a new screening and selection cascade for hit generation of compounds active against the blood-stage of P. falciparum.