The goals of this subproject are to take a research program that has been strong and provide collaborative support with research intensive faculty from other campuses. The venom research program is at a stage in its development when it would benefit from collaboration with major universities with excellent facilities and faculty with expertise in molecular biology. The natural resistance of certain animals to snake venoms is well documented in the literature. These animals have antihemorrhagic and antiproteolytic factors in their sera which neutralize a wide variety of hemorrhagins found in many snake venoms. The research goals are to isolate and determine if antihemorrhagins in opossum serum could be used to neutralize venom in humans and other animals without causing complications. The objectives in the next five years are to focus on the following questions. (a) Can venom be used to increase the natural antihemorrhagin titer or stimulate antibody production in opossums? (b) What organ or tissues(s) in the opossum are producing antihemorrhagins? (c) Do other resistant animals (woodrats and Mexican ground squirrels) neutralize venom in the same way? (d) Can a non-animal assay such as an ELISA or western blot be used to screen for antihemorrhagins found in other resistant animals? (e) What is the smallest segment of the opossum antihemorrhagin that can neutralize the hemorrhagins found in snake venoms? (f) Will a smaller segment (less than 10,000 Daltons) neutralize venom without causing serum sickness or other anaphylactic problems in snakebite victims? (g) Does the smaller segment neutralize all seven hemorrhagins in C. atrox venom? (h) Do the seven hemorrhagins found in snake venom have a common active site that bind to the antihemorrhagins? (i) Do the antihemorrhagins found in other resistant animals bind and neutralize venom hemorrhagins in a similar manner? (j) Can DNA probes and primers be made by sequencing the N terminal end of antihemorrhagins? (k) Can these probes and primers be used to identify and clone antihemorrhagic genes and can the genes be expressed in E. coli? and (l) can the recombinant product (antihemorrhagin) be used to neutralize snake venoms? Two faculty from TAMUK will be working on the subproject II, and collaboration agreements with other universities have been established in the areas of molecular biology and immunohistology.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR011594-04
Application #
6123356
Study Section
Project Start
1998-09-30
Project End
1999-09-29
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Texas A&M University-Kingsville
Department
Type
DUNS #
City
Kingsville
State
TX
Country
United States
Zip Code
78363
Salazar, Ana Maria; Guerrero, Belsy; Cantu, Bruno et al. (2009) Venom variation in hemostasis of the southern Pacific rattlesnake (Crotalus oreganus helleri): isolation of hellerase. Comp Biochem Physiol C Toxicol Pharmacol 149:307-16
Galan, Jacob A; Sanchez, Elda E; Rodriguez-Acosta, Alexis et al. (2004) Neutralization of venoms from two Southern Pacific Rattlesnakes (Crotalus helleri) with commercial antivenoms and endothermic animal sera. Toxicon 43:791-9
Sanchez, Elda E; Ramirez, Maria Susana; Galan, Jacob A et al. (2003) Cross reactivity of three antivenoms against North American snake venoms. Toxicon 41:315-20
Sanchez, Elda E; Galan, Jacob A; Perez, John C et al. (2003) The efficacy of two antivenoms against the venom of North American snakes. Toxicon 41:357-65
McKeller, Morgan R; Perez, John C (2002) The effects of Western Diamondback Rattlesnake (Crotalus atrox) venom on the production of antihemorrhagins and/or antibodies in the Virginia opossum (Didelphis virginiana). Toxicon 40:427-39
Perez, J C; McKeller, M R; Perez, J C et al. (2001) An internet database of crotaline venom found in the United States. Toxicon 39:621-32
Sanchez, E E; Soliz, L A; Ramirez, M S et al. (2001) Partial characterization of a basic protein from Crotalus molossus molossus (northern blacktail rattlesnake) venom and production of a monoclonal antibody. Toxicon 39:523-37
Martinez, R R; Perez, J C; Sanchez, E E et al. (1999) The antihemorrhagic factor of the Mexican ground squirrel, (Spermophilus mexicanus). Toxicon 37:949-54
Ramirez, M S; Sanchez, E E; Garcia-Prieto, C et al. (1999) Screening for fibrinolytic activity in eight Viperid venoms. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol 124:91-8
Perez, J C; Sanchez, E E (1999) Natural protease inhibitors to hemorrhagins in snake venoms and their potential use in medicine. Toxicon 37:703-28

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