The Genomics, Disease Ecology and Global Health Strategic Research Investment Program and the Eck Institute for Global Health have announced the presentation of nine awards to support pilot projects in the areas of genomics and bioinformatics. This is the second round of funding for pilot projects to be performed in Notre Dame’s recently expanded core facilities in genomics and bioinformatics. The goal of this investment is to provide University-wide access to technical and computational resources for high throughput, computationally intensive genomics and bioinformatics projects, as well as to recruit new scientific users to these powerful technologies. In support of this goal, applications for pilot project funds to support scientist from across campus for whom genomics and/or bioinformatics could be important to their research were solicited and reviewed. Projects were selected based on scientific significance and rationale, approach, preliminary data, need for support and the potential to leverage additional extramural funding.
The awards include:
Patricia Champion from the Department of Biological Sciences – to identify new factors that are associated with hyper-virulence in mycobacteria. Mycobacterium tuberculosis is the causative agent of the global Tuberculosis epidemic, which kills nearly two million people annually and latently infects one in three people worldwide. Studies will be performed using M. marinum as a model for the mechanisms of virulence of the human pathogen. Understanding how mycobacteria modulate pathogenesis, both positively though virulence factors and negatively through anti-virulence factors is essential in our efforts to prevent and treat Tuberculosis.
Jeffrey Feder from the Department of Biological Sciences – to identify genetic markers that identify local and regional populations of Wuchereria bancrofti, the parasite the causes filariasis, and sometimes results in a debilitating disease known as elephantiasis. The markers developed in the pilot project will be used in future studies to assess the genetic structure of local and regional population of parasites on Haiti to provide critical information for determining whether and on what scale mosquito and/or human movement coupled with non-compliance issues may compromise mass drug administration strategies targeted to eliminate disease. The work in Haiti will be performed in conjunction with the ongoing Haiti program lead by Dr. Thomas Streit at Notre Dame.
Jeffrey Feder from the Department of Biological Sciences – to use the Bioinformatics Core expertise to assist in interpreting sequencing data for various species of Rhagotletis fly. This information will assist in the development of an on site, chip-based, rapid identification platform for use in orchards. From a basic science perspective, an important issue in evolutionary biology is the degree to which the genome differentiates during the early stages of speciation. Rhagoletis is a model for speciation in action in the face of gene flow via host plant shifting.
Paul Huber from the Department of Chemistry and Biochemistry - to study the role of small ubiquitin-like modifier (SUMO) proteins during embryogenesis. The levels of expression of over 30,000 genes will be measured in Xenopus embryos in which the SUMOylation pathway has been disabled. These studies will rapidly identify perturbations in transcription due to the inhibition of the SUMO pathway, with the goal of understanding how key developmental regulators are controlled by this process.
Shaun Lee from the Department of Biological Sciences – to address how Group A Streptococcus (GAS) is able to resist the effects of its own toxin. GAS is one of the world’s most successful pathogens, causing a multitude of common infections such as pharyngitis, cellulitis and impetigo. It is also responsible for more severe diseases such as rheumatic fever, necrotizing fasciitis, and toxic shock syndrome. It produces a powerful toxin that is capable of killing many different cell types. These studies will produce insights into how toxin-producing microorganisms achieve resistance against the effects of their own toxin and could uncover important therapeutic targets to combat these toxin virulence factors.
Mary Ann McDowell from the Department of Biological Sciences – to further elucidate the regulation of key cellular activities in cells infected by Leishamania spp. L. donovani and L. major are intracellular parasites that cause visceral and cutaneous leislmaniasis, respectively. These are among the neglected diseases that place a major burden on health in developing countries. The goal of this research is to enhance our understanding of how these parasites modulate the human immune response to avoid immune destruction.
Richard Taylor from the Department of Chemistry and Biochemistry – to identify the key steps in the biosynthesis of gephyronic acid, a natural product isolated from a bacteria that has been shown to inhibit growth of yeast and mold, as well as a range of mammalian cell types. Identification of the gene cluster responsible for biosynthesis will be used to develop an expression system which will provide an alternative source of larger quantities of the natural product. This will allow further biological evaluation of gephyronic acid as an antibiotic or cancer drug.
Molly Duman Scheel from the Indiana University School of Medicine, South Bend – to study the role of Drosophila Deleted in Colorectal Cancer (DCC) gene in signaling pathways that are associated with the induction of cancer. The Drosophila imaginal discs are excellent systems in which to study cell growth and invasive migration, and will be used as a model in these studies. In humans, both mutation of DCC, as well as increased expression of its ligand (netrin) have been linked to a variety of cancers. These experiments will yield new information about the signaling pathways inducing cancer in response to modulations in DCC signaling.
Andrew Mahon from the Department of Biological Sciences – to survey the population genetics of Bythotrephes longimanus – Ponto Caspian spiny water flea – and establish a relationship between patterns of human movement and genetic variation in inland lake populations of B. longimanus. The Ponto Caspian spiny water flea is an invasive species that was introduced into the Great Lakes and has begun to appear in inland lakes in Canada and the U.S., with the potential to disrupt lake ecology, especially culturally and economically important sport fish populations. Increased understanding of its spread will help limit these impacts.