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dc.contributor.advisorBurleigh, Barbara
dc.contributor.authorMarcenac, Perrine
dc.date.accessioned2019-08-08T12:28:39Z
dash.embargo.terms2019-05-01
dc.date.created2018-05
dc.date.issued2018-05-02
dc.date.submitted2018
dc.identifier.citationMarcenac, Perrine. 2018. Molecular and ecological factors modulating the fitness of Anopheles gambiae mosquitoes infected with Plasmodium falciparum. Doctoral dissertation, Harvard University, Graduate School of Arts & Sciences.
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41126978*
dc.description.abstractPlasmodium parasites are the causative agent of human malaria, a disease that despite global efforts of eradication still infects over 200 million people and kills hundreds of thousands of people every year. Transmission of this disease relies on the infectious bite of more than 50 different mosquito species of the genus Anopheles that occupy diverse geographic and ecological niches. This global distribution enables malaria transmission to occur on nearly every continent, yet not all species are alike in their capacity to efficiently transmit this parasite. Indeed, vectorial capacity shows remarkable interspecies heterogeneity due to a host of biological processes within the mosquito that can impact Plasmodium survival but also modulate vector fitness. Moreover, individual Anopheles lineages have experienced different degrees of pressure from human Plasmodia and their ancestral species due to geographic variation in disease burden over millions of years. Such heterogeneity may be reflected by different evolutionary signatures present in the mosquito genome, enabling the discovery of mosquito factors or molecular processes that may have been shaped by Plasmodium infection. In this dissertation, we examine the response of Anopheles gambiae, the major malaria vector in sub-Saharan Africa, to infection with the deadliest human malaria parasite, Plasmodium falciparum. Given An. gambiae’s high reproductive rate and unique mating biology, we focus particularly on the reproductive fitness of this species in an effort to elucidate components of its biology that contribute to vectorial capacity. Through this work, we gain significant insight into molecular and physiological processes that impact An. gambiae fitness in the face of infection and may have been shaped by P. falciparum. Furthermore, we identify ecological factors that affect the An. gambiae-P. falciparum interaction, potentially modulating mosquito resistance to infection and impacting transmission dynamics in the field. After a review of the literature on the Anopheles-Plasmodium association in Chapter 1, in Chapter 2 we perform studies on the role of Mating-Induced Stimulator of Oogenesis (MISO), a female protein produced in reproductive tissues in response to sexual transfer of the steroid hormone 20-hydroxyecdysone (20E), in limiting the fitness costs inflicted by P. falciparum infections on female reproductive output. We first examine the reproductive fitness of Anopheles species from different geographical regions and from different evolutionary lineages infected with these malaria parasites. These analyses show that while important vectors like An. gambiae and Anopheles stephensi that have experienced considerable long-term pressure from P. falciparum do not suffer a cost to infection, the Central American vector Anopheles albimanus which has had a more recent association with this malaria species produces fewer eggs when fed on an infectious blood meal. Moreover, we determine that the tolerance to P. falciparum infection observed in An. gambiae is at least partially due to the function of MISO, and that MISO likely acts within 20E-mediated signaling cascades at the interface of blood feeding- and mating-induced pathways that maintain female reproductive fitness. As the evolution of MISO within the Anopheles genus appears to have been driven by differential transfer of male 20E during mating, specific evolutionary trajectories of post-mating processes in various Anopheles subgenera may have contributed to their differential ability to support Plasmodium parasites. Importantly, these studies reveal a previously unknown link between two 20E-regulated processes, hypoxia-induced molting and egg development, that may impact both reproductive success and Plasmodium development. In Chapter 3, we turn our focus from tolerance to resistance mechanisms in An. gambiae by determining the effects of the endosymbiotic bacteria Wolbachia on P. falciparum and on its mosquito host. We find that the Wolbachia species wAnga that infects Anopheles populations from West Africa negatively correlates with Plasmodium in field-captured mosquitoes. Laboratory-based studies, however, do not show a striking effect of wAnga on P. falciparum, suggesting the ecological context of natural Anopheles populations may be critical to wAnga’s potential anti-plasmodial effects. This body of work expands our understanding of the molecular and physiological processes in Anopheles that contribute to vectorial capacity and tolerance to infection, and highlights how ecological pressures imposed on natural populations affect parasite survival within the mosquito and may have shaped the evolution of vector-parasite interactions.
dc.description.sponsorshipBiological Sciences in Public Health
dc.format.mimetypeapplication/pdf
dc.language.isoen
dash.licenseLAA
dc.subjectvector-parasite interactions
dc.titleMolecular and ecological factors modulating the fitness of Anopheles gambiae mosquitoes infected with Plasmodium falciparum
dc.typeThesis or Dissertation
dash.depositing.authorMarcenac, Perrine
dash.embargo.until2019-05-01
dc.date.available2019-08-08T12:28:39Z
thesis.degree.date2018
thesis.degree.grantorGraduate School of Arts & Sciences
thesis.degree.grantorGraduate School of Arts & Sciences
thesis.degree.levelDoctoral
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy
thesis.degree.nameDoctor of Philosophy
dc.contributor.committeeMemberRubin, Eric
dc.contributor.committeeMemberNeafsey, Daniel
dc.contributor.committeeMemberHarrington, Laura
dc.type.materialtext
thesis.degree.departmentBiological Sciences in Public Health
thesis.degree.departmentBiological Sciences in Public Health
dash.identifier.vireo
dash.author.emailperrine.marcenac@gmail.com


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