Mosquitoes serve as vectors for diseases including dengue and malaria, for which half the world's population is at risk. Mosquito-borne pathogens are transmitted during blood feeding, yet despite its crucial role in pathogen transmission, blood feeding behavior remains ill understood. The sensory integration of physical and chemical cues on the skin and below its surface, and the effect of pathogen infection on blood feeding are poorly characterized. These knowledge gaps are due to a lack of tools to quantitatively study blood feeding behavior. To overcome these limitations, I propose an innovative approach to study blood feeding by leveraging quantitative imaging, computer vision, and an engineered human skin mimic to create a high-throughput behavioral assay. Imaging mosquitoes feeding on a transparent skin mimic will enable the detailed characterization of the behavioral trajectory leading to blood feeding while simultaneously allowing the analysis of biting dynamics by imaging the expectoration of saliva. To unravel the behavioral effects of pathogen infection, I will compare blood feeding by non-infected Aedes aegypti (the main dengue vector) and Anopheles gambiae (an important malaria vector) with their dengue virus and Plasmodium falciparum infected counterparts. Next, I will use microfabricaton to embed artificial vasculature in the skin mimic to dissect the sensory cue integration underlying blood feeding. I will characterize the biting dynamics of mutant Aedes aegypti deficient in various sensory pathways feeding on skin mimics that present a defined set of cues. By combining my skills in biophysics with the host labs expertise in mosquito-pathogen interactions, this project will provide a deep understanding of the neurobiology underlying blood feeding by mosquitoes, and the effect that pathogen infections may have on this behavior. Elucidating the transmission of mosquito-borne pathogens will provide valuable insights to combat mosquito-borne diseases.
Antiretroviral therapy can decrease HIV-1 below the limit of detection but fails to eliminate the virus completely. One of the main goals of a HIV-1 vaccine is the generation of cytotoxic CD8 T cell responses that counteract the virus. CD8 T cells participate in the control of viremia early but progressively show weakened functions, which leads to loss of virus control. HIV controllers are a rare group of infected patients who can control the virus for years without antiretroviral therapy. CD8 T cells from HIV-controllers display an outstanding capacity to eliminate infected CD4 T cells ex vivo but the underlying mechanisms are still not understood. Preliminary data aiming at establishing a single cell transcriptional signature associated with control of HIV suggest an important role of the mTOR pathway during the chronic stage. This pathway plays a major role in glucose metabolism and CD8 T cells cytotoxic function. This raises the hypothesis that the extraordinary HIV-suppressive capacity of HIV-controllers CD8 T cells is associated with the modulation of mTOR pathway and glucose metabolism. This project aims to 1) Study the single cell gene expression of HIV-specific CD8 T cells in HIV patients longitudinally from acute to chronic stages and understand the factors linked to control and loss of function of CD8 T cells during disease progression. 2) To characterize the role of mTOR pathway in the ability of CD8 T cells from HIV-controller to eliminate infected cells and test if this pathway can be modulated to fine-tune anti-HIV CD8 T cells responses. 3) To understand if an optimal glucose metabolism is necessary for CD8 T-cells suppression of HIV and if this capacity can be improved by increasing available glucose. This work will help to understand the characteristics of effective CD8+ T cell responses against HIV and may guide the development of anti-HIV vaccines or immunotherapies to induce HIV controller-like responses in HIV-infected progressors.