Flea head, nerve cord, hindgut and malpighian tubule nucleic acid molecules, proteins and uses thereof

Abstract

The present invention relates to flea head, nerve cord, hindgut and Malpighian tubule proteins; to flea head, nerve cord, hindgut and Malpighian tubule nucleic acid molecules, including those that encode such flea head, nerve cord, hindgut and Malpighian tubule proteins; to antibodies raised against such flea head, nerve cord, hindgut and Malpighian tubule proteins; and to compounds that inhibit flea head, nerve cord, hindgut and Malpighian tubule protein activity. The present invention also includes methods to obtain such proteins, nucleic acid molecules, antibodies, and inhibitory compounds. Also included in the present invention are therapeutic compositions comprising proteins, nucleic acid molecules, antibodies, or protective compounds derived from proteins of the present invention as well as the use of such therapeutic compositions to protect animals from flea infestation. Also included in the present invention is the use of flea head, nerve cord, hindgut and Malpighian tubule proteins to derive inhibitory compounds.

What is claimed is:  
     
         1 . An isolated nucleic acid molecule expressed by a tissue selected from the group consisting of a flea HMT tissue and a flea HNC tissue, identified by a method comprising: (a) constructing a cDNA library enriched for HMT or HNC expressed sequences; and (b) identifying a nucleic acid molecule in said library.  
     
     
         2 . The nucleic acid molecule of  claim 1 , wherein said nucleic acid molecule comprises a nucleic acid sequence selected from the group consisting of a nucleic acid sequence of Table I and a nucleic acid sequence of Table II.  
     
     
         3 . An isolated nucleic acid molecule that hybridizes to a nucleic acid sequence selected from the group consisting of a nucleic acid sequence of Table I, a nucleic acid sequence of Table II, a nucleic acid sequence complementary to a nucleic acid sequence of Table I, and a nucleic acid sequence complementary to a nucleic acid sequence of Table II, under conditions comprising (a) hybridizing in a solution comprising 1×SSC in the absence of helix destabilizing agents, at a temperature of 37° C. and (b) washing in a solution comprising 1×SSC in the absence of helix destabilizing agents, at a temperature of 47.5° C.  
     
     
         4 . The nucleic acid of  claim 3 , wherein said nucleic acid molecule comprises a nucleic acid sequence that is at least 70% identical to a nucleic acid sequence selected from the group consisting of a nucleic acid sequence of Table I and a nucleic acid sequence of Table II.  
     
     
         5 . The nucleic acid of  claim 3 , wherein said nucleic acid molecule comprises a nucleic acid sequence selected from the group consisting of a nucleic acid sequence of Table I and a nucleic acid sequence of Table II.  
     
     
         6 . A recombinant molecule comprising a nucleic acid molecule as set forth in  claim 3  operatively linked to a transcription control sequence.  
     
     
         7 . A recombinant virus comprising a nucleic acid molecule as set forth in  claim 3 .  
     
     
         8 . A recombinant cell comprising a nucleic acid molecule as set forth in  claim 3 .  
     
     
         9 . A method to produce a protein, said method comprising (a) transfecting a host cell with a nucleic acid molecule of  claim 3  to produce a recombinant cell; (b) culturing the recombinant cell under conditions effective to produce said protein in said recombinant cell; and (c) recovering the protein.  
     
     
         10 . The method of  claim 9 , wherein said nucleic acid molecule comprises a nucleic acid sequence that is at least 70% identical to a nucleic acid sequence selected from the group consisting of a nucleic acid sequence of Table I and a nucleic acid sequence of Table II.  
     
     
         11 . The method of  claim 9 , wherein said nucleic acid molecule comprises a nucleic acid sequence selected from the group consisting of a nucleic acid sequence of Table I and a nucleic acid sequence of Table II.  
     
     
         12 . An isolated protein selected from the group consisting of: an isolated protein encoded by a nucleic acid molecule that hybridizes to a nucleic acid sequence selected from the group consisting of a nucleic acid sequence complementary to a nucleic acid sequence of Table I and a nucleic acid sequence complementary to a nucleic acid sequence of Table II, under conditions comprising (a) hybridizing in a solution comprising 1×SSC in the absence of helix destabilizing agents, at a temperature of 37° C. and (b) washing in a solution comprising 1×SSC in the absence of helix destabilizing agents, at a temperature of 47.5° C.  
     
     
         13 . The protein of  claim 12 , wherein said nucleic acid molecule comprises a nucleic acid sequence selected from the group consisting of a nucleic acid sequence of Table I and a nucleic acid sequence of Table II.  
     
     
         14 . The protein of  claim 12 , wherein said nucleic acid molecule comprises a nucleic acid sequence that is at least 70% identical to a nucleic acid sequence selected from the group consisting of a nucleic acid sequence of Table I and a nucleic acid sequence of Table II.  
     
     
         15 . An isolated antibody that selectively binds to a protein as set forth in  claim 12 .  
     
     
         16 . A method to identify a compound capable of inhibiting activity of an isolated protein of  claim 12 , said method comprising contacting an isolated protein of  claim 12  with a putative inhibitory compound under conditions in which, in the absence of said compound, said protein has activity; and determining if said putative inhibitory compound inhibits said activity.  
     
     
         17 . A kit to identify a compound capable of inhibiting activity of an isolated protein of  claim 12 , said test kit comprising an isolated protein of  claim 12  and a means for determining the extent of inhibition of said activity in the presence of a putative inhibitory compound.  
     
     
         18 . A composition comprising an excipient and an isolated nucleic acid molecule of  claim 3 .  
     
     
         19 . A composition comprising an excipient and an isolated protein of  claim 12 .  
     
     
         20 . A composition comprising an excipient and an isolated antibody of  claim 15.