Summer Undergraduate Program

Dr. Brown’s lab studies the immune response to influenza virus and strategies to enhance current vaccines. The summer project will investigate the ability of adjuvants, in combination with conserved and conjugated influenza antigens to provide universal protection against different influenza strains. We will use ELISA assays to detect antibody to vaccine antigens as well as flow cytometric assays to study T cell responses to influenza proteins in vaccinated mice.

The student who works on this project will have broad exposure to the theory and practice of microbiology and molecular genetics, specifically as they relate to efforts to discover new therapies for mycobacterial infections, including those caused by Mycobacterium tuberculosis and Mycobacteriodes abscessus. Techniques for bacterial culture and monitoring of growth will be applied in drug screening assays to characterize the activity of known and experimental antimicrobial compounds. Genetic engineering tools will be employed to create bacterial strains with targeted gene deletions and reporter constructs. The student will have the opportunity to learn about Next Generation Sequencing approaches such as RNAseq, which will be used to determine the mechanism of action of experimental compounds. Bioinformatic analysis of genomic and transcriptomic data will allow incorporation of these data into models of drug mechanism. There will be opportunities to explore predictive models of antimicrobial efficacy, including within macrophages and mouse models. All hands-on work will be conducted at BSL2 using M. abscessus or attenuated M. tuberculosis strains.

Dr. Chojnacki’s laboratory is focused on the discovery, characterization and optimization of novel antimicrobial therapeutics that target previously unexploited molecular mechanisms.

Due to increasing rates of drug resistance, new antibiotics are urgently needed to treat mycobacterial infections, including Mycobacterium abscessus (Mab) and Mycobacterium tuberculosis (Mtb), the deadliest infectious disease in human history. We have identified several small molecules with favorable drug-like characteristics that inhibit Mtb through novel molecular mechanisms, and therefore hold promising potential in mitigating common drug resistance mechanisms. Using techniques in microbiology, genetics, molecular biology and biochemistry, students will work to help decipher the novel molecular targets of these molecules and assist in understanding their mechanisms of action.

This summer we will be testing drug candidates for ADMET properties, which are key determinates in the success of a drug. ADMET is an acronym for absorption, distribution, metabolism, excretion, and toxicity. These properties ultimately predict if the drug will get to the target tissue at an appropriate concentration with a sufficient exposure duration. They can also predict off-target effects associated with safety concerns. While these properties can be tested in various ways in the lab, it is increasingly common to test these properties using mathematical models that consider the chemical structure of the molecule. This summer we will test some of the free models available to cross-validate their performance. To do this, we will curate a dataset from databases that describe ADMET properties in well studied drugs. We will then apply the models to our dataset and perform statistical tests to assess which models perform best. We can also subclassify the drugs in our dataset to see if specific models perform better in specific chemistry spaces or indications.

Dr. Reiley is an immunologist with an independent research laboratory at Trudeau Institute. The major objective of his research is to advance our understanding of the generation and maintenance of CD4 T cell immunity during acute and persistent infections, including influenza, herpes virus and Mycobacterium tuberculosis (Mtb) infections. Current studies focus on understanding how a history of prior infections impact the immune response to vaccination or subsequent infection, specifically regarding subsequent influenza virus infections and live-attenuated influenza virus vaccines. The summer project in Dr. Reiley’s Group will be focusing on a new area of interest, Mucosal Associated Innate T (MAIT) cells after Mtb vaccination. The main questions outstanding are whether MAIT cells can be induced by vaccines, and what is their primary role in protection against infection?

Enteroviruses (EVs) are small, non-enveloped RNA viruses that replicate primarily in the human gut and are spread via fecal-oral transmission. Some EVs, such as poliovirus, can escape the gut and infect other tissues leading to severe disease. For poliovirus, infection of motor neurons leads to paralytic poliomyelitis, a life-threatening disease that has been nearly eradicated through the use of vaccines. This project will focus on an EV that is currently a significant human health concerns: EV-D68. EV-D68, unlike other EVs, has evolved to be transmitted via the respiratory route, causing mild to severe cold-like symptoms. EV-D68 has also been associated with less frequent but severe neurological disease manifestations, including encephalitis and acute flaccid paralysis. How host genetic variation might impact replication and disease for these EVs is unknown. To address this, genetically distinct mouse embryonic fibroblast (MEF) cell lines will be screened for susceptibility to EV-D68 using traditional virological methods, including plaque assay and TCID50 assay. This work may lead to useful new mouse models of EV infection that could be used to evaluate therapeutic and/or vaccine-based medical countermeasures.