MUTATION DETECTION IN HEMOCHROMATOSIS CANDIDATE GENES

The program has been divided into two phases according to the guide lines for the Physician Scientist Award (K11) program and will be completed over a period of five years. The Phase I will focus on acquiring fundamental knowledge and basic laboratory skills required for advanced work in molecular genetics. The didactic portion will include laboratory meetings, research conferences, and formal course work in molecular biology of eukayotic cells, developmental biology and advanced topics in molecular genetics. Her research during this phase will involve analysis of 10 novel cDNA clones that she isolated from the region of the hemochromatosis gene locus. This work will include methods to identify the most likely gene candidates for hemochromatosis by mutation detection in Southern and Northern blot analysis, and gene expression studies involving iron regulation. The transition from Phase I to Phase II will consist of a formal presentation of research progress and demonstration of a broad fund of knowledge acceptable to the advisory committee. During Phase II the great bulk of the applicant's time will be spent in the laboratory. Emphasis will be placed on developing self confidence and independence in the use of scientific methodology. She will continue to analyses the cDNA clones. During this period she will undertake to master advanced techniques of mutation detection such as SSCP. RNase protection, DGGE, and sequencing. She will have to isolate full length clones for some of the genes by library screening. In the process she will acquire sufficient laboratory skills and knowledge to pursue an independent research career and develop an efficient method of screening additional gen candidates as they become available.