Graduate students present at 2016 Health Sciences Research Week

Monday, April 18, 2016

The 2016 Health Sciences Research Week is a three day event that focuses on graduate research.  The following Microbiology graduate students participated in the poster session: Ashley Cooney, Amber Ford, Lauren Kinkead, Tiffany Lim, Nurbek Mambetsariev (MSTP/Interdiscipli-
nary Graduate Program in Immunology) Alexandra Paharik, Kayley Schulmeyer and Lori Wheeler (MSTP/Interdisciplinary Graduate Program in Immunology).

Nurbek Mambetsariev has been selected as one of the 2016 poster session winners in the Carver College of Medicine Student Category. Poster Title: Loss of TRAF3 Promotes a Premalignant metabolic State in B cells.  Nurbek works in Microbiology Professor Gail Bishop's lab.

Lauren Kinkead has been selected as one of the winners in the Iowa City VA Health Care System Student Category. Her mentor is Lee-Ann Allen in Internal Medicine. Poster title: Elucidation of the mechanism of apoptosis inhibition by Francisella tularensis.

Below are selected poster and research descriptions:  

Ashley Cooney: The goal of our work is to design a gene therapy vector that could serve as a single treatment for cystic fibrosis (CF).  CF is a genetic disease in which affected individuals have chronic pulmonary inflammation and bacterial lung infections.  In our studies, we designed a hybrid nonviral/viral vector called piggyBac/AAV carrying the CFTR (cystic fibrosis transmembrane conductance regulator) gene.  We delivered piggyBac/AAV-CFTR to newborn CF pigs (developed at the University of Iowa) and quantified phenotypic correction using various metrics. We observed a change in anion channel current, an increase in tracheal pH, and rescued the bacterial killing defect compared to untreated CF pigs.  These studies provide exciting evidence for advancement of this vector into preclinical trials.

Tiffany Lim: My poster is on my work studying bacterial co-infections in cutaneous leishmaniasis. Cutaneous leishmaniasis is a disease transmitted by a sand fly that causes nodular lesions on the skin that ulcerate and take many months to resolve with severe scarring. Ulceration appears to have an important role in healing, as patients treated prior to ulceration often have prolonged disease compared to patients treated after ulceration. Since secondary bacterial infections in cutaneous leishmaniasis ulcers is quite common, we hypothesized that bacteria present on the skin during parasite inoculation or ulceration activate a greater inflammatory response than Leishmania alone. We utilize a mouse skin co-inoculation model to study the effects of Staphylococcus aureus co-infection on disease due to L. major.

Nurbek Mambetsariev: Our work focuses on the adapter protein TRAF3 and its role in regulating B cell survival and oncogenesis. TRAF3 deficient B cells can survive substantially longer in vitro and in vivo. We showed that in the absence of TRAF3, B cells are metabolically reprogrammed leading to utilize more glucose via oxidative phosphorylation and anaerobic glycolysis. These cells also require glucose to sustain their survival.

Alexandra Paharik: The project I presented is "Staphylococcus caprae produces a novel inhibitor of Staphylococcus aureus quorum sensing and virulence." We show that the S. caprae Type I autoinducing peptide (AIP) inhibits S. aureus quorum sensing and prevents the progression of a murine skin infection of MRSA. We also report the structure of the S. caprae AIP, which was identified by mass spectrometry. I also was selected for a trainee talk during research week to present this project. 

Kayley Schulmeyer (Her abstract):  CsrA family RNA-binding proteins are widely distributed in bacteria and regulate gene expression at the post-transcriptional level. Pseudomonas aeruginosa has a canonical CsrA family member (RsmA) and a novel, structurally distinct variant (RsmF). To better understand RsmF binding properties, we performed parallel systematic evolution of ligands by exponential enrichment (SELEX) experiments for both RsmA and RsmF. The initial target aptamer was a 57 nt RNA transcript containing a central core randomized at 15 sequential positions. Most of the selected aptamers were the expected size and shared a common consensus sequence (CAnGGAyG). Concatemerized aptamers (80-140 nts) containing two consensus-binding sites were also identified. Representative short (single consensus site) and long (two consensus sites) aptamers were tested for RsmA and RsmF binding.  Whereas RsmA bound the short aptamers with high affinity, RsmF was unable to bind the same targets. RsmA and RsmF both bound the long aptamers with high affinity. Mutation of either consensus GGA site in the long aptamers reduced or eliminated RsmF binding, suggesting a requirement for two binding sites. Based on our observations that high affinity binding by RsmF appears to require two binding sites, we used an in-silico approach to search for candidate RsmF targets in the P. aeruginosa genome. We queried a library of 5’ UTRs for potential targets of RsmF based on the number and positions of GGAs, and secondary structure. Experimental validation of potential targets yielded few direct targets for both RsmA and RsmF indicating that more than sequence and structure contribute to differential binding.

Lori Wheeler: My poster title was "Inhibition of CSF1R signaling exacerbates mouse hepatitis virus infection." Microglia are the CNS-resident mononuclear phagocytic cells typified by a unique ramified shape and distinctive gene expression. At steady-state, the blood brain barrier separates microglia from the other mononuclear phagocytic cells. In cases of neuroinflammation that result in extensive mononuclear cell infiltration, studies of true microglia are difficult because activated microglia are indistinguishable from infiltrating mononuclear phagocytic cells. My poster describes a model for studying bona fide microglia using CSF1R-mediated depletion of microglia and shows that depletion of microglia dramatically increases the lethality of a neurotropic mouse hepatitis infection.