BIOCHEMICAL ISOLATION OF PEPTIDES: ROLE IN MENTAL HEALTH

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DESCRIPTION (from applicant's abstract): Peptides related by a C-terminal FLRFamide affect behavior, including panic attack and anxiety. Thus, perturbations in FLRF amide peptide signaling may lead to abnormal mental activity. Although FLRFamide peptides play a role in mental health, their sites of synthesis, regulation of expression and transduction mechanisms are not known. Numerous FLRFamide peptides have been isolated, however no FLRFamide peptide and gene has been identified from a genetically tractable mammal. Thus, the proposed goal is to isolate mouse FLRFamide and delineate its role in mammalian physiology. The proposed hypothesis is that an FLRFamide peptide exists in mouse, a human model system amenable to molecular genetics research, and that the peptide plays a critical role in behaviors. The proposed hypothesis is supported by the following: 1) isolate a mouse FLRFamide peptide, 2) the presence of FLRFamide immunoactivity in mammalian brain, and 3) the structural and functional homology between vertebrate and invertebrate peptides. The principal investigator will test the hypothesis with the following aims: 1) isolate a mouse FLRFamide peptide, 2) clone the mouse FLRFamide cDNA and gene, and 3) determine the distribution of the moue FLRFamide peptide. The investigator will achieve these aims by: 1) purifying an FLRFamide immunoreactive material from a mouse brain homogenate, 2) amplifying the FLRFamide transcript from mouse brain mRNA and screening a mouse genomic library, and 3) raising antisera to the mouse FLRFamide peptide. Accomplishing these aims is crucial to the foundation of the interdisciplinary study to decipher the role of FLRFamide in human physiology. The future research will utilize the power of a molecular genetics approach to generate knockouts and transgenic mice, establish bioassays, and isolate interactive molecules to confirm function, elucidate regulation of expression, and delineate signaling. The proposed research provides the basis of the future design of FLRFamide agonists and antagonists, and assays for mass screening of pharmacological compounds and clinical tests relevant to human health.