Molecular basis of malaria transmission by mosquitos
The Billker lab develops new genetic technologies to investigate how malaria parasites reproduce in mosquitoes and get transmitted.
Understanding how malaria parasites get transmitted holds one of the keys to preventing the disease from spreading. Since transmission is closely linked with sexual reproduction, it is also at the heart of how the parasites evolve through recombining their genes. How Plasmodium species transition between host and vector and how they use cues from their hosts to time mating and reproduction has always fascinated me.
These biological questions still drive much of my work, but I also realise that answers will come more easily, the better we can engineer the parasite’s genome. Together with my colleagues at the Wellcome Sanger Institute, Julian Rayner and Marcus Lee, we therefore continue to invest heavily into new technologies that are beginning to reveal gene functions in malaria parasites at unprecedented scale. We are keen to share these tools and resources widely, since we realise how useful they will be to understand the disease and to find new targets for drugs and vaccines.
Having spent much of the past years designing and running a DNA engineering pipeline, we are pleased that the PlasmoGEM project has produced vectors for the deletion of almost half of all Plasmodium berghei genes. It is now easy to make large numbers of mutants, each identified through its own molecular barcode. Importantly, barcodes allow us to screen mutants for specific phenotypes and we are excited to think about all the new possibilities this creates.
To identify new gene functions we often combine mutated parasites with a very detailed analysis of all their transcripts, proteins or protein modifications. With our collaborators this has allowed us to find a master regulator of sexual development and mosquito transmission, and to define a new pathway that regulates many key events in the parasite’s life cycle.
Most recently my laboratory has been awarded an € 2.5 million ERC Advanced Grant for my project: ”Sex in malaria parasites - from genome scale functional gene profiling to transmission blocking intervention targets” and a SEK 30 million project grant from the Knut and Alice Wallenberg Foundation for my research project "The systematic identification or parasite gene functions essential for malaria transmission by mosquitoes using forward genetic screens and single cell phenotyping."
More information on the website of the Billker lab: www.billkerlab.org
Information about PlasmoGem: https://plasmogem.sanger.ac.uk/
Photo credit: Mattias Petterson.