1542A Thomas Hall

Campus Box 7615
North Carolina State University
Raleigh, NC 27695
919.515.7081 (office)
919.515.3641 (lab)
919.515.7867 (fax)

MB 490
Senior Seminar in Microbiology



Hosni M. Hassan

Oxidative Stress

Biographical Sketch

Hosni Hassan was born in Alexandria, Egypt. He became interested in science and mathematics during his high school years. In 1959, Hosni received his B.Sc. degree in agriculture/food science/microbiology from the University of Ain Shams, Cairo. He worked for two years as a teaching assistant and research associate before he was awarded an Egyptian Scholarship to study for his Ph.D. in microbiology with minors in biochemistry and food microbiology at the University of California, Davis. After graduating in 1967 Hosni continued at Davis doing postdoctoral work on lactic acid bacteria. He returned to Egypt in November 1968 to assume the position of assistant professor of microbiology and biochemistry at Cairo High Polytechnical Institute. In 1970, he moved to the University of Alexandria where he taught courses in enzymology, microbial physiology, and dairy microbiology. In 1972, he went to McGill University in Canada as a visiting professor. In 1974, Hosni moved to the University of Maine (Orono) where he taught general microbiology and researched the production of methane from chicken manure and the expression of alkaline phosphatases in marine bacteria. In 1976, he moved to Duke University to work on the biosynthesis and the biological roles of superoxide dismutases and hydroperoxidases. Hosni left Duke in 1979 to accept a tenured associate professorship in the Microbiology and Immunology Department in the Medical School at McGill University, Canada. He came to North Carolina State University in 1980 as an associate professor of food science and microbiology in the Department of Food Science. He was promoted to professor in 1984 and also became an associate member of the departments of toxicology and biochemistry. He has taught courses in microbial physiology, food microbiology, microbial toxins, biochemistry, and free radicals in toxicology. Hosni spent one year as a senior Fulbright Scholar at the University of Paris (France) working on the genetics of the manganese superoxide dismutase gene in Escherichia coli. In 1992, he became a member of the Biochemistry Department. In 1993, he became head of the Department of Microbiology. His research continues to be in the fields of free radical biology and the molecular regulation of the antioxidant enzymes in prokaryotes and unicellular eukaryotes.

Research Brief

Oxygen free radicals are both toxic and mutagenic. Therefore, knowing how cells protect themselves from the many catastrophic effects of oxygen free radicals will have an impact on our understanding of aging, cancer, and cellular damages caused by oxidant stress.

We have established that the expression of the sodA gene which encodes the Mn++-containing superoxide dismutase (MnSOD) in E. coli is tightly controlled by the level of superoxide radical, the concentration of iron in the cells, and the redox state. These observations lead us to postulate that the regulation of MnSOD biosynthesis is under negative control by an iron- containing regulatory protein where iron plays the role of a redox sensor. To identity the repressor gene(s) and product(s), we isolated anaerobically derepressed sodA mutants using strains containing sodA-lac Z gene fusions. We were able to obtain and characterize cis and trans-acting regulatory mutations. Also, by using site-directed mutagenesis we identified the operator site of the sodA gene. The data, thus far, support our model (i.e. negative control via an iron- containing repressor), but it shows that the regulatory circuit is much more complicated than originally thought. Thus, we found four trans-acting regulatory elements that act in concert to regulate the level of MnSOD in response to various environmental stimuli. The four regulatory elements are FUR (Ferric Uptake Regulation), ARC (Aerobic Regulatory Control),FNR (Fumarate-Nitrate Regulation), and IHF (Integration Host Factor). It is noteworthy that both Fur and Fnr are iron©containing proteins. We also demonstrated the role of iron and managnese in the maturation of MnSOD and will study the interactions of these repressors with the operator region of sodA and how the four repressors communicate with each other.

Future research goals are to see if the regulation of MnSOD in other prokaryotes and eukaryotes is similar to that of E. coli. We are also interested in studying the physiology and control(s) for the synthesis of hydroperoxidases and the iron©containing superoxide dismutase of E. coli and other prokaryotes.