The long term goal is to become a successful basic scientist in the field of molecular biology through an individually designed and structured program. This includes an intense didactic curriculum (Phase I) in combination with a specific research project (Phase II). The research of interest is to determine the structure of the gene(s) coding for mucin(s) which are secreted by normal and malignant lung cells and to understand the mechanisms that regulate them. These airway glycoconjugates are believed to have a critical role in protecting the lungs from foreign substances and pathogens but little is known about the molecular interactions that regulate the syntheses, secretion, or clearance of mucins. Another unexplored arena is their role in the development of pulmonary disease. Of interest is their significance in the pathogenesis of lung cancer which is the most common and lethal cancer in the United States. Evidence exists to support the hypotheses that alteration of the mucin/proteoglycan structure or the regulation of their genes may influence tumor development. This research will provide basic information about mucin biosynthesis. Cultured cell lines derived from human squamous lung carcinomas provide an ideal source of different human airway glycoconjugates. Recombinant cDNA clones in the pBR322 or lambda gtll systems of mRNA obtained from the above lung cancer clones will be constructed and those coding for the protein cores of the airway mucins will be selected using specific oligonucleotide probes or specific antibodies. The cloned cDNAs will be sequenced and the organization of this sequence used to derive the amino acid sequence of the protein cores and their subunit structures. This work will then provide the basis for investigating the regulation of these genes.
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