Opportunities for pre-doctoral and postdoctoral training in the lab.

Current projects are well funded by NIH research grants continuously awarded to Dr. Papermaster from NEI since 1975. A new award from the Foundation Fighting Blindness supports some of the most recent work on transgenic frogs as well. All facilities for molecular biology and fluorescence and electron microscopy are contained in the lab or are provided by excellent core facilities at UCHC in nearby labs. The group usually contains 3 or more post-docs/graduate students and several technicians. Several graduate students also rotate through the laboratory for short research periods as part of the Program in Neuroscience. Projects are designed to promote independent research so that they become candidates for faculty positions.

Prior post -docs and graduate students now include a Senior Scientist at the La Jolla Cancer Research Institute (Dr. Michiko Fukuda), a Dean of Basic Sciences at the New England College of Optometry (Dr. Mark Zorn), Professors at the University of Strathclyde, Scotland (Dr. Carolyn Converse), University of Wisconsin (Dr. Art Polans), University of North Texas Medical School (Dr. Michael Chaitin), an Associate Professor at the LSU Medical School (Dr. Barbara Schneider), an Associate Professor at the University of North Texas Medical School (Dr. Neeraj Agarwal) and an Assistant Professor at the University of Michigan (Dr. Dusanka Deretic).

Applicants should contact Dr. Papermaster at dsp@sun.uchc.edu and provide a resume summarizing training, publications and references.

Studies in this area are described in greater detail in the web pages.

Current projects:

Biosynthesis and polarized sorting of membrane proteins in photoreceptors. Using the XOP promoter, we can restrict high level expression of transgenes to rods. Vectors with appropriately placed multiple cloning sites have been generated to readily allow preparation of transgenic constructs with a very large array of genes. In just our first year and a half we have studied 50 transgenic frog lines using over 25 different constructs, sometimes several in a week. These experiments proceed quite quickly because the frog eye matures in the first week after fertilization and no breeding is needed to characterize the effects of the transgene. Longer term studies of larger numbers of frogs are possible since the transgenes are passed to offspring.

Apoptosis of photoreceptors and its amelioration.

The mutant proteins can induce rod apoptosis and some may also induce cone death in transgenic frog retinas. Thus these frogs have provided us with new models of human retinal degeneration in a retina which more closely resembles the human retina since the frog, unlike the mouse, has a abundant cones. We hope to gain insight into diseases such as retinitis pigmentosa and macular degeneration with these models. The frog eye can be sustained in tissue culture and thus the potential for pharmacologic inhibition of apoptosis can be envisioned.

Synaptic protein biosynthesis:

These experiments are being planned with colleagues at Yale University. Our intent is to use the XOP promoter to express various membrane proteins of the synaptic terminal and to ascertain domains that control sorting and transport of synaptic proteins to the opposite end of the cell from the outer segment. This exploits the potential of analysis of neural cell differentiation in vivo in ways which can only be partially evaluated in neuronal tissue culture. Since the cell we study differentiates in its normal environment, the cues for sorting are fully provided by the in situ environment while the ease of generation of the transgenic frogs rivals that of transfection of cultured cells.

The environment of the laboratory.

Our lab is part of a new Department of Neuroscience organized at the University of Connecticut Health Center in Farmington, CT. Farmington is a suburb of Hartford and is 45 min. from New Haven and an hour and a half from Boston and New York. It is in the foothills of the Berkshire Mountains and benefits from the mild climate of Southern New England. Public education systems in the area are recognized nationally for excellence.

The Program in Neuroscience at UCHC includes many scientists involved in sensory systems research including a group of 6 vision scientists studying the molecular biology of rhodopsin, inheritance of glaucoma, central processing, and ocular immune privilege. The Medical School includes strong groups involved in fundamental aspects of molecular and cell biology and development which interact closely with our group to accelerate research progress.