The life history traits of parasites are dependent on the host environment and host immune response. Heligmosomoides bakeri, is an intestinal nematode parasite that infects laboratory mice (Mus musculus). This investigation used rapamycin, an immunosuppressant drug, in the diet of the host. Rapamycin is currently being considered as an over the counter drug to extend life expectancy. The purpose of this experiment was to determine if inhibition of the host immune system by rapamycin had a significant effect on parasite life history traits during a secondary infection. Mice were fed either a rapamycin diet or control diet for two months. Mice were then infected with H. bakeri, drug cleared of the primary infection, then re-infected with a secondary H. bakeri infection. Starting eight days after the secondary infection fecal egg counts were done daily to determine worm reproduction in vivo. Eighteen days after the secondary infection the mice were euthanized and worms were removed, sexed and counted. Length of ten female and ten male worms from each mouse was then measured, and 10 females were cultured to measure ex vivo reproduction. After 24 hours of incubation in culture media, egg output and worm motility (an index of viability) were measured. For this experiment I was involved in recording the worm length and was responsible for performing the ex vivo egg count and motility measurements. Results will provide important information about potential over-the-counter use of rapamycin in humans to slow biological aging and how changes in immune function may affect susceptibility to parasite infection.

Age related immune decline may play a role in susceptibility to parasitic helminth infections among the octogenarian population. Few studies have examined very old age on susceptibility to helminth infections in people. Effects of age on host susceptibility using mouse models also has not been thoroughly studied for older ages of laboratory mice (Mus musculus), such as beyond about one year. In this study, the intestinal nematode (Heligmosomoides bakeri), a model for hookworm infection in humans, was used to infect 1-year-old and 2-year-old Swiss Webster mice. At 40 days post-infection, worms were removed and worm survival, sex ratio, ex vivo egg output, and worm length (as an index of growth) were measured and analyzed. I expect to find an increase in worm survival, ex-vivo egg output, and worm length in older mice. These results will be valuable because they will model the helminths capacity to proliferate in older hosts in comparison to younger hosts during a human hookworm infection.

Small insect-inspired robots have much potential in exploration and have been experiencing a wave of innovation in recent years. Small robots have promise especially in space exploration where each kilogram costs $10,000 to launch, but tiny robots tend to weigh under a gram. However, some problems persist, such as difficulty with landing after flight and hopping mechanisms wearing down after a few uses. Our work focuses on developing a hopping robot that is capable of attaching to an overhanging surface when it jumps and that has durable mechanisms to optimize the number of jumps per bot. The hooking mechanism differs from previous work, usually electrostatic patches, and instead is inspired by the hooked feet of beetles, which is lighter and does not require constant electrical power. For optimizing jumps, we are working to develop a jumping body constructed from and designed for carbon fiber rather than the previously used fiberglass. Carbon fiber has a higher strength to weight ratio and is more elastic than fiberglass, making it efficient for flight and the repetitive motion carried out by the body when bent by the onboard actuator. All designs are created using an iterative design process where parts are micromachined and assembled, then tested for desired qualities. From this, we are aiming to develop an autonomous hopper capable of completing multiple jumps and grabbing without maintenance on any part of the bot.

During HIV infection, CD8+T-cells are crucial for the control of viral replication. Increased CD8+T-cell polyfunctionality, which is the ability for one cell to perform more than one function within the immune response, was associated with improved clinical outcomes, is now the focus of experimental curative therapies for HIV. One therapy that showed promise is a Conserved Elements DNA (CE) vaccine, which is designed to prime the immune system with essential regions of the virus, thereby eliciting polyfunctionality and circumventing escape mutants. A novel immunotherapeutic combinatorial approach was investigated for the ability to reduce or eliminate viral burden in Simian Human Immunodeficiency Virus (SHIV) infected macaques receiving antiretroviral drug therapy. We evaluated effects of this regimen on CD8+T-cell polyfunctionality and its correlation to viral control after analytical antiretroviral treatment interruption (ATI). Our combinatorial immunotherapy regimen uses the CE vaccine to target highly conserved viral sequences, latency reversal agent GS986, exhaustion reversal agent anti-PD-1, and CCR5 gene editing to delete the co-receptor for viral entry in CD4+T-cells. Analysis of CD8+T-cell polyfunctionality was performed using intracellular cytokine staining and flow cytometry to measure the frequency of CD8+T-cells secreting one or more of the following effector functions: TNFα, IFNγ, IL-2, and both CD107a and Granzyme B. Polyfunctionality induced by the combinatorial regimen was algorithmically quantified and compared to a control group receiving no interventions and a group receiving CE vaccine and CCR5 gene editing alone. Our analysis showed neither significant differences in polyfunctionality between treated and control groups, nor any changes in polyfunctionality within the subset of CD8 targeting conserved regions of the virus. However, we observed diverse viral control post-ATI among all animals, and additional experiments are in progress to determine if CD8 polyfunctionality played a role in improved viral control post-ATI.

There is a critical lack of knowledge regarding the effects of human immunodeficiency virus (HIV) and zika virus (ZIKV) coinfection in respect to ZIKV pathogenesis, vertical transmission and current vaccine strategies. ZIKV has received global attention because of its clinical complications including congenital malformations during vertical transmission and Guillain-Barré syndrome, a neurocognitive disorder in adults. Recently, ZIKV outbreaks have occurred in tropical and subtropical regions endemic with HIV, therefore it is imperative to understand the impact HIV-ZIKV coinfection may have when moving forward with ZIKV vaccine design. Furthermore, in humans and non-human primates (NHPs) frequencies of blood monocytes increase during HIV and simian immunodeficiency virus (SIV) infection and monocytes are early targets of ZIKV infection. Therefore, we hypothesize that cells from HIV infected individuals have the capacity to harbor increased ZIKV replication and could lead to enhanced ZIKV viremia and pathogenesis. For this study, we use a NHP model to determine the impact of acute SIV infection on ZIKV pathogenesis. We determine ZIKV cellular targets in the blood and preliminary results show an increase in NHP blood monocyte within the first six weeks of SIV infection. We evaluate whether SIV infection increases the susceptibility of cells to ZIKV infection by isolating cells from SIV- and SIV+ animals, infecting them in vitro with ZIKV, and assessing viral replication by plaque assay. Our preliminary findings suggest that in vitro ZIKV replication may increase in cells from SIV+ NHP blood when compared to SIV- blood. Future studies will look at the impact of SIV infection on in vivo ZIKV replication and whether ZIKV replication is enhanced in cells from HIV-infected individuals.

Efforts to engineer flying micro-robots (~50mg) are motivated by their potential advantages relative to larger robots, such as greater deployment numbers at the same cost. There are significant developments in flapping wing robots at insect-scale; however, little advancement has been made in the development of robots with ionic actuation using electrohydrodynamic (EHD) thrust. This thrust is generated through the ionization of air particles and momentum transfer of these positive ions with neutral air molecules. EHD thrusters have used collector grids and emitter wires to generate a thrust for controlled flight. In this research, we design and fabricate a 1.8 x 2.5 cm micro-thruster that weighs a total of 43 mg including the carbon fiber collector grid, four blue tempered steel emitters, and eight fiber optic glass tubes. This robot is hand-assembled using a laser fabricated external fixture. Electrodes of the robot are fabricated using a laser based system. The whole robot takes a total of 20 minutes to assemble. Emitters are supplied with a high voltage (~2.5kV) using a bundle of 51-gauge insulated copper wires. Similar wire is used for grounding the collector grid. A parametric study is carried out to optimize the physical parameters of the robot. Experiments performed in this research show that the thrust generated is larger than the weight of the robot.