The Center for Global Infectious Disease Research has funded five initial projects deemed to be catalytic because they are innovative, have short time lines, demonstrate the potential for new funding and promote new collaborations between the center’s researchers and laboratories. Congratulations to the awardees!

Understanding Host Cell Responses to the Hemolytic Lipid Toxin of Group B Streptococcus

Researchers in the Rajagopal and Kaushansky labs are investigating the mechanisms of cell death in macrophages and neutrophils, and cell survival in dendritic cells, in response to a hemolytic pigment produced by Group B streptococcus (GBS) bacteria. Understanding the cell survival mechanisms could provide novel insight into curtailing GBS pathogenesis, which is the leading cause of bacterial infections during pregnancy and can cause fetal injury, stillbirth, preterm birth, and early onset infections in newborns. The data generated as part of this study will accelerate a newly formed collaborative partnership between our laboratories, which have already resulted in a grant submission.

Transcriptome-Driven Inference of Adverse Drug Interactions

The Hernandez and Sherman labs propose to establish a computational model to predict drug interactions that promote or mitigate toxicity in the human host/patient. By adapting INDIGO (Inferring Drug Interactions using chemo-Genomics and Orthology) to build an “INDIGO-Tox” model based on drug-induced hearing injury data generated from an animal system, the researchers hypothesize that they can harness the underlying approach to predict potentially toxic drug interactions in humans. INDIGO-Tox represents the first step toward rapid preclinical assessment of putative adverse drug interactions. Successful completion will establish a clear path to extend prediction into other organ toxicities and will directly generate hypotheses for translation into humans.

Single-Cell Profiling of Plasmodium Vivax Sporozoites

Researchers in the Aitchison and Kappe labs are testing a hypothesis about the origin of dormant liver stage forms (hypnozoites) during malaria infection. They hypothesize that anopheline mosquitoes infected with the malaria parasite Plasmodium vivax (P. vivax) deliver parasites with two predetermined transcriptional programs: one leads to active replicating liver stages and the other remains as dormant liver hypnozoites. Using a single-cell RNA-seq (scRNA-seq) method, the team will investigate potentially distinct P. vivax hypnozoite forming populations. This pilot study will be used as a basis for future grant applications exploring parasite behavior, with the long-term goal of targeting dormancy with novel drugs and vaccine candidates.

Single Cell Genome and Transcriptome Profiling of HIV-Infected Cells that Comprise the HIV-1 Reservoir

Researchers in the Sather, Wagner and Frenkel labs are testing a hypothesis about what drives the persistence of infected HIV-1 cells during antiretroviral therapy (ART). As HIV-1 infected cells are rare in number, the team believes that high-throughput single-cell studies are needed to examine their hypothesis. Their research objective is to develop a novel microfluidics high-throughput strategy for single cell analysis of DNA and RNA from HIV-infected cells.

Single-Cell Transcriptome Analysis of Leishmania-Infected Macrophages

The Myler and Sather labs are applying recent advances in single-cell genomics to elucidate the changes in gene expression that occur in individual parasites during infection of macrophages and differentiation into amastigotes, as well as examining how different macrophages respond to infection. Comparison of the transcriptome profiles obtained from individual Leishmania cells will answer several questions that have been difficult to resolve using conventional approaches. These findings will provide preliminary data for subsequent R21 and/or R01 grant proposals to dissect the process in more detail, as well as the interrogation of human clinical samples.