1 / 2

(Project Title ) Grant Number

(Project Title ) Grant Number. Project Objective : What is the purpose of the overall effort and significance to the goals of CounterACT (1-3 concise sentences)? Technological Approach : In brief general terms, what are you going to do and how will you do it (4-5 concise sentences)? . 3. 1.

elani
Télécharger la présentation

(Project Title ) Grant Number

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. (Project Title ) Grant Number Project Objective: What is the purpose of the overall effort and significance to the goals of CounterACT (1-3 concise sentences)? Technological Approach: In brief general terms, what are you going to do and how will you do it (4-5 concise sentences)? 3 1 Figure(s)/data illustrating significant/exciting new progress or KEY results of the work performed in the current year (include exposure paradigm if in vivo results are illustrated) • Specific Aims (as listed in application): 4 2 Figure(s)/data illustrating significant/exciting new progress or KEY results of the work performed in the current year (include exposure paradigm if in vivo results are illustrated) Key Challenge(s): POC: PI Name/Institute and email address

  2. Enhancing the anti-OP activity of the XYZ enzyme R21 NS012345-01 -30 min 0 +1 min ~8 min ~40 min 24 h Project Objective: To develop an effective in vivo therapeutic (bioscavenger) against organophosphate (OP) intoxication, to include pesticide and chemical warfare agent poisonings. Technological Approach: Based on computational studies, site-directed mutagenesis will be utilized to generate mutants of the human XYZ enzyme. Mutants will then be expressed and biochemically assayed for catalytic activities against common substrates (phenyl acetate and paraoxon) in vitro. Optimal mutants will be characterized against bona fide nerve agents in vitro. Mutant enzymes with at least 10-fold enhancement in anti-nerve agent activity will be evaluated as potential bioscavengers in animal studies. Definitive analytical methods will be developed as needed throughout the research process. AMN (2.0 mg/kg i.m.) Seizure Onset Diazepam (10 mg/kg i.p.) and/or Test Drug Survival HI-6 (125 mg/kg i.p.) 1.6 LD50 GD (180 ug/kg s.c.) Legend description of figures, tables, etc. . . . Experimental Paradigm Specific Aims (as listed in application): Use scanning mutagenesis, substrate/inhibitor binding, and functional analysis to determine the role of specific amino acid residues within the active site. Identify 10 amino acid residues involved in catalytic machinery Generate 5 mutant XYZ enzymes with at least 10-fold enhanced activity for organophosphorus compounds. Description of key results . . . • Key Challenge(s): • To develop an expression system that would yield large quantity of functional recombinant XYZ enzymes POC: Dr. Larry Jones; UNV; jonesl@unv.edu

More Related