Parasitic diseases still plague broad swaths of the world’s developing countries, reducing childhood survival rates and stunting economic growth. However, genome sequence data for the pathogens involved and funding from various organizations give new hope of controlling or even eliminating these diseases. Dr. Anderson focuses on the genetic basis and evolution of biomedically important traits in two of the most important human groupsof parasites:
- Malaria parasites (~655,000 deathsper year)
- Parasitic blood fluke (Schistosomaspecies) responsible for schistosomiasis (~200,000 deathsper year)
Dr. Anderson has30 yearsof experience working in parasitology.
Inside The Lab
Malaria infects around 300 million people each year, killing ~655 thousand people. No vaccine exists, and by now, parasite resistance to all five classesof antimalarial drugs has been reported. We use several different strategies to identify genes that underlie drug resistance and to better understand drug resistance evolution. Our lab closely collaborates with cliniciansworking on the Thailand- Myanmar border and with researchersin Malawi.
- As the malaria genome is relatively small, whole genome sequence information from populations of parasites can be studied. We are using genomic analysis of field-collected parasitesand genetic crosses conducted in humanized mice to identify drug resistance genes and better understand drug resistance evolution.
- Change in gene copy number is an important and understudied cause of resistance in pathogens. By examination of copy number variation, we have alreadycharacterized an important gene involved in drug resistance.
- Gene editing methods using CRISPR/Cas9 now allow us to introduce specific changesto the malaria parasite genome, so we can experimentally investigate the effects of specific mutations.
Using the approaches listed above,we are addressing several fundamental questionsabout drug resistance evolution: How many times has drug resistanceevolved in nature? What genes are involved? What is the role of copy number variation and single nucleotide polymorphisms? What is the rate of mutation? What is the impact of resistance geneson parasite fitness? Answering these questionscould help identify drug targets and novel interventions against malaria.
Schistosomiasis is caused by blood flukes (Schistosoma spp.). These parasites infect over 270 million people in Africa, South America and Asia, and utilize snail intermediate hosts. The adult worms live in the laboratory. Our lab has pioneered the use of genetic crosses between schistosomes in the laboratory for identifying the genetic basis of biomedically important parasite traits. We have used this approach, together with exome sequencing, to identify the precise mutations that underlie oxamniquine resistance, and are now applying the same approach to understand praziquantel resistance, host specificity, parasite virulence, and multiple other important biomedical traits.
The complete parasite lifecycle is maintained at Texas Biomed, using colonies of snail intermediate host, and hamsters or mice in place of humans for the vertebrate stage of the parasite lifecycle. We collaborate closely with Dr. Philip LoVerde at the University of Texas Health Science Center, as well as with colleagues in London (UK), Perpignan (France), Kenya, Uganda, and Brazil.
Main Technologies And Methods Used
- RNA-Sequencing/Quantitative PCR and RT-PCR
- Single cell genomics/FACs
- SNP genotyping
- Malaria parasite culture and growth assays
- CRISPR/Cas9 gene editing
- Custom exome sequencing (schistosomes)
- Schistosome lifecycle maintenance
- Linkage mapping in experimental crosses