In the Carlton lab, we use the tools of comparative genomics – whole genome sequencing and genomics, bioinformatics, molecular biology and population genetics – to study the biology and evolution of closely related strains or species of parasite. In medicine and global public health, the term parasite is used to describe a group of eukaryotic microbes and helminths that cause some of the world’s most devastating diseases. The parasites that we study include:
(1) Species of the malaria parasite Plasmodium: more than half the world’s population is at risk from malaria, and the disease causes ~216 million cases and ~655,000 deaths per year. The most deadly form of the parasite, Plasmodium falciparum, is found mostly in sub-Saharan Africa where it causes the deaths of children < 5 years old. Plasmodium vivax is the most common species outside Africa in South America and Southeast Asia, and is closely related to a group of species that infect Asian Old World monkeys from Taiwan to Sri Lanka, called the monkey malaria clade.
Map of malaria distribution. Picture Credit: World Malaria Report 2005
(2) The sexually transmitted parasite Trichomonas vaginalis and related trichomonads: T. vaginalis is the most common non-viral STI, and causes ~249 million cases per year world-wide. It is associated with increased risk of HIV-1 infection, and serious complications during pregnancy. Other trichomonads include Trichomonas tenax found in the mouth, Pentatrichomonas hominis a zoonotic gut parasite, and Tritrichomonas foetus a serious venereal pathogen that causes abortion in cattle.
T. vaginalis parasites adhering to pink vaginal tissue.Image courtesy of Antonio Pereira-Neves and Marlene Benchimol, Santa Ursula University, Rio de Janeiro, Brazil
(3) Other fascinating parasites such as species of the enteric pathogen Cryptosporidium, the bovine parasite Theileria, and Babesia.
Our research often begins with generation of a resource such as sequencing, assembly and annotation of a parasite’s genome. For example, we have been involved in the sequencing of P. falciparum , species of rodent malaria (Plasmodium yoelii yoelii , Plasmodium chabaudi chabaudi and Plasmodium berghei ), several strains of P. vivax [4, 5], several strains of the monkey malaria Plasmodium cynomolgi , and the first T. vaginalis genome .
Sequencing the genome of a parasite enables the complete gene and protein repertoire to be identified and provides a wealth of data about the basic biology of that organism, leading to hypothesis-driven studies. Generating sequences of multiple strains or species enables studies of whole genome evolution, genetic diversity and population genetics/genomics. Some of the research areas that members of the Carlton lab undertake in these areas include:
- Developing polymorphic genetic markers from sequenced genomes to determine the genetic diversity and population structure of extant parasites, or for association mapping of parasite traits, for example:
- genetic diversity and population structure of T. vaginalis in New York City STD clinics
- identifying genetic determinants of metronidazole resistance in T. vaginalis
- developing a global genetic diversity map of P. vivax
- population genetics of P. cynomolgi in Southeast Asia
- genetic epidemiology of P. falciparum and P. vivax in India
- Using molecular and cell biology to investigate the presence, function and mechanism of groups of genes identified in a parasite’s genome sequence, for example:
- determining the function of meiosis-specific genes in nominally asexual T. vaginalis
- function and evolution of transposable element families in species of trichomonad
- prevalence, diversity and function of the TVV virus in T. vaginalis
Since many of the parasites we work on are important global public health problems in lower and middle income countries as well as poor regions of the United States, we collaborate with researchers and clinicians who work in public health clinics in order to move our research from the bench to the field. Some examples of our collaborations include:
- Center for the Study of Complex Malaria in India, with the National Institute of Malaria Research of the Indian Council of Medical Research, New Delhi
- Population genetics of T. vaginalis in India, with Professor Nancy Malla, PGMRI, India
- T. vaginalis repeat infections among HIV negative women, with Dr Patty Kissinger, Tulane University of Louisiana
- Development of new T. vaginalis diagnostic tests with BioHelix, Atlas Genetics and PATH
- Gardner, M.J., et al., Genome sequence of the human malaria parasite Plasmodium falciparum. Nature, 2002. 419(6906): p. 498-511.
- Carlton, J.M., et al., Genome sequence and comparative analysis of the model rodent malaria parasite Plasmodium yoelii yoelii. Nature, 2002. 419(6906): p. 512-9.
- Hall, N., et al., A comprehensive survey of the Plasmodium life cycle by genomic, transcriptomic, and proteomic analyses. Science, 2005. 307(5706): p. 82-6.
- Carlton, J.M., et al., Comparative genomics of the neglected human malaria parasite Plasmodium vivax. Nature, 2008. 455(7214): p. 757-63.
- Neafsey, D.E., et al., The malaria parasite Plasmodium vivax exhibits greater genetic diversity than Plasmodium falciparum. Nat Genet, 2012. 44(9): p. 1046-50.
- Tachibana, S., et al., Plasmodium cynomolgi genome sequences provide insight into Plasmodium vivax and the monkey malaria clade. Nat Genet, 2012. 44(9): p. 1051-5.
- Carlton, J.M., et al., Draft Genome Sequence of the Sexually Transmitted Pathogen Trichomonas vaginalis. Science, 2007. 315(5809): p. 207-212.