(One intermediate revision by the same user not shown)
Line 24:
Line 24:
</font size>
</font size>
|}
|}
'''MRC Career Development Fellowship Abstract of Research'''
<br>
Understanding the molecular basis of mosquito susceptibility to Plasmodium infection and thus malaria transmission is fundamental to implementing vector-based malaria control strategies. To date, genotypic interactions between Anopheles gambiae and Plasmodium falciparum, the deadliest of the human malarias, have only been examined in one study. This work detected that genotype-by-genotype (g*g) interactions were the major determinants of the outcome of infection such that no parasite genotype was able to infect all mosquito families, and likewise, no mosquito family was able to resist all parasite genotypes. This finding highlights the complexity of the interaction and motivates research particularly aimed at dissecting the molecular basis of g*g interactions: which molecules lead to different infection outcomes due to their genetic variation?
I will use genome-wide association studies (GWAS) in the two major sub-Saharan African malaria vectors, A. gambiae and A. arabiensis, to map genetic variation associated with P. falciparum susceptibility. Lab mosquitoes will be infected with different combinations of recently collected Senegalese parasites that will constitutively express green or red fluorescent protein, allowing the infection success of individual parasite genotypes to be assessed when mosquitoes are fed mixtures of two parasite genotypes. Field mosquitoes will be fed parasites from local gametocyte carriers. GWAS will be carried out using a genotyping chip that interrogates 400,000 SNPs in the mosquito genome. By comparing susceptible to refractory mosquitoes, small regions of the mosquito genome associated with large impacts on the outcome of the infection will be identified. Candidate genes falling in these regions and potentially involved in mosquito susceptibility will be phenotypically characterised using RNA-interference gene knockdown techniques.
The molecular nature of g*g interactions and the role of mosquito species in P. falciparum susceptibility is crucial to examine because success of any vector control strategy will depend on application to all of the malaria vectors. Molecules found to be consistently involved in infection outcomes become prime targets for transmission blocking interventions, such as drugs and vaccines. Targeting mosquitoes is an effective malaria transmission reduction strategy as evidenced by the historical and current successes of insecticides and bednets. However, insecticides and bednets will fail as mosquitoes evolve insecticide resistance and bednet avoidance. New vector-based malaria control strategies will depend on a deep understanding of the molecular interactions between vectors and parasites. The efforts described here will further our understanding of the connection between genotype and phenotype in a system that is of great human interest.
'''Other research interests and active projects'''
<br>
In collaboration with Dan Neafsey (Broad Institute), Seth Redmond (Imperial College), and Danny Park (Broad Institute), I have developed an Anopheles gambiae SNP chip that interrogates 400,000 positions across the genome of Anopheles gambiae and 1000 positions across the genome of Plasmodium falciparum. Thus far, we have used the chip to investigate population structure in M, S, and Bamako mosquitoes from Mali.
I have also used the SNP chip to carry out genome-wide association studies (GWAS) mapping genetic variation contributing to the outcome of Plasmodium falciparum infections. Additionally, I am helping several graduate students in the Christophides lab to use the SNP chip to carry out additional GWAS mapping genetic variation contributing to the outcome of Plasmodium berghei LRIM knockdowns (Leanna Upton), Beauveria bassiana (Jo Fernando), Onyongyong virus (Jo Fernando), and Serratia marcescens (Stavros Stathopolous) infections. All of these projects are actively ongoing and producing exciting results, identifying both genes we already know to be involved in response to infections and genes we did not know about. Thus, GWAS in mosquitoes are opening new avenues of research.
I am also interested in understanding the genetic basis of the speciation process. To investigate the genetic basis of speciation in the Anopheles gambiae group, we analyzed whole genome sequence data from M and S colonies and found extensive divergence genome-wide in spite of ongoing hybridization in nature. It is from these sequences that we identified the 400,000 variable positions which we chose to examine on the SNP chip (below).
Line 72:
Line 54:
evolutionary genetics, sexual conflict, sexual selection, host-parasite antagonistic coevolution, genetic conflict, evolvability, population genetics/genomics, drosophila, anopheles, plasmodium, cephalopods & nepenthes.
evolutionary genetics, sexual conflict, sexual selection, host-parasite antagonistic coevolution, genetic conflict, evolvability, population genetics/genomics, drosophila, anopheles, plasmodium, cephalopods & nepenthes.
<br>
<br>
<br>
'''Previous appointments'''
<br>
University College London. BBSRC funded postdoctoral researcher. 2004- 2006.
Education
University of California, Davis. Ph.D. in Population Biology. 2000- 2004.
Advisor: Dr. David Begun.
University of Texas, Austin. First year Ph.D. program in Integrative Biology. 1999-2000.
Advisors: Dr. James Bull & Dr. David Begun.
University of Michigan, Ann Arbor. Bachelor of Science with High Honors in Biology. 1993-1997. Advisors: Dr. Shawn Meagher & Dr. Philip Myers.
Teaching
Guest lecturer for the Advanced Topics in Cellular and Molecular Immunology course led by George Christophides.
My lectures are on Population genomics and Genome-wide association studies.
Teaching assistant at UCDavis for Population genetics (2003, 2004) and Evolution (2001,2002)
Topics and systems of interest
evolutionary genetics, sexual conflict, sexual selection, host-parasite antagonistic coevolution, genetic conflict, evolvability, population genetics/genomics, drosophila, anopheles, plasmodium, cephalopods & nepenthes.
Publications
This link to PubMed lists my publications.
