The research objective of this work is to develop a dextran-peptide conjugate that selectively binds injured tissue surfaces to form a protective colloid barrier against trauma-induced inflammatory cell damage to healthy tissues. This therapy could have a tremendous impact on the morbidity and mortality rates of many pathological processes.
Aim 1 : To synthesize and characterize several anti-inflammatory bioconjugate formulations.
Aim 2 : To perform in vitro assays to verify biochemical and biological function of the dextran-peptide conjugates.
Aim 3 : To determine the influence of the bioconjugate on leukocyte-endothelium interactions in vivo using rat mesenteric venules stimulated by TNF-a. The training involved in this appointment will equip the applicant with the skills necessary to perform state-of-the-art research in molecular therapeutics. This field is a new direction from the applicant's chemical engineering and biophysical chemistry training, and will work synergistically in the long run with the previous training. When the appointment is completed, the applicant will be well-qualified to perform research integrating molecular therapeutics and ultrasensitive analysis as an independent researcher. Over the four-year duration of this award, areas of work will include didactic coursework, training """"""""at the bench"""""""" at Arizona State University in Tempe, Arizona and intravital microscopy training with Dr. Stuart Williams at The University of Arizona in Tucson, Arizona. For the entire duration of this project 100% of the applicant's time will be spent working on the proposed work and training activities. A projected timeline of the tasks that will be performed each year is listed below. Year 1: didactic coursework, synthesis of the bioconjugates, binding affinity measurements of the bioconjugates, training in the responsible conduct of research; Year 2: didactic coursework, in vitro testing of bioconjugates, manuscript preparation; Year 3: training in animal surgery, intravital microscopy training, preliminary in vivo testing of the optimal bioconjugate, manuscript preparation; and Year 4: in vivo testing of the optimal bioconjugate and manuscript preparation.
