His laboratory uses state-of-the-art multidimensional NMR spectroscopy along with computer aided molecular modeling to solve structural and dynamics problems in molecular pharmacology, rational drug designing, protein folding and solution phase biostructure. They are interested in utilizing structure of peptides, proteins, enzymes, receptors and acceptors as templates in drug designing. They are also interested in developing programs and routines for computer aided structure and conformation elucidation. Once an accurate model is determined, they use it as a template for design of appropriate constrained peptide ligands. In summary, the integration of above mentioned knowledge such as structure-function and molecular recognition may play a key role for the successful design of pharmaceuticals in the future. Furthermore, these studies can guide the design of future experiments, particularly that employing recombinant DNA technology to create new protein structures useful in developing resistance to insects and diseases in plants and animals.
Three projects are being studied by the members of the Tomich Lab. 1) Design, synthesis and testing of anion selective channel forming peptides to determine the mechanism by which channels can show ion selective and still have extremely high transport rates. The object of this research is to develop a sequence that could be used to provide a new chloride conductive pathway in cystic fibrosis patients. 2) Characterization of a peptide that causes a transient yet repeatable disruption of tight junctions in barrier membranes. The goal of this project is to test this peptide’s ability to open barrier membranes and facilitate drug delivery. 3) Design and synthesis of peptides with unusually high adhesive strength. The goal of this project is to design a biodegradable protein sequence that could be introduced and ultimately harvested from crop plants for use in the plywood industry.
Research Areas include Evolution of gene regulatory networks, using segmentation in the red flour beetle, Tribolium castaneum as a model system, Genomics and Bioinformatics, focusing on genome sequence analysis Tribolium.
COBRE benefits greatly from Dr. DeLisle’s participation in the program. As a member of the University of Kansas faculty, Dr. DeLisle provides a unique perspective, adding breadth to COBRE planning and activities. The focus of his research is investigation of pathobiology of cystic fibrosis (CF) in the gastrointestinal (GI) system. Using the Cftr knockout mouse (Cftr tm1UNC) model of CF they are investigating the inter-related roles of excessive mucus, abnormal bacterial growth, and impaired motility in the pathophysiology of CF in the intestine. Pharmacological and dietary approaches are being used to determine the mechanisms of intestinal dysfunction in CF. The long term goal is to provide new therapeutic interventions to improve intestinal function in CF. This work includes in vivo and in vitro studies; morphological and immunocytochemical techniques; and measurement of mRNA and protein levels for various inflammatory markers and signaling molecules.
Dr. Picking's laboratory explores the molecular mechanisms by which enteric bacterial pathogens cause disease. More specifically, they examine the proteins secreted by important diarrheal pathogens in terms of their structure, function, and potential interactions with host cells. The long-rang goal of the Picking laboratory group is to determine the precise functional and structural organization of IpaC and to elucidate the molecular and structural basis for IpaC interaction with and subversion of epithelial cell signaling molecules. Picking is working to determine the sequence, structural and physical features present in the IpaC N-terminal domain that are involved in its translocation to the host cell membrane. His group is determining the molecular basis for the role of the IpaC C-terminus in directing vascular escape of internalized Shigella and subverting the host cell signals that control the host cell cytoskeleton. They are also striving to generate crystals ( or co-crystals) of IpaC and IpaC fragments for high-resolution structure analysis.
Dr. Takemoto’s laboratory is studying the role of protein kinase C isoforms in control of gap junctions and in repair during diabetes. Diabetes results in a loss of protein kinase C gamma from both lens and retina, resulting in changes in gap junction control. This contributes to damage seen during diabetic cataract and retinopathy. Her laboratory is also studying the role of food antioxidants which contribute to protection from cancer and from damage during diabetes.