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Control of cell growth and death

Achievement/Results

Thesis research by IGERT student Jennifer Rochira produces a potential new molecule that could be used to treat cancer or degenerative diseases through the programmed cell death pathway.

Programmed cell death, also called apoptosis, is a normal cellular process that leads to the orderly destruction, or death, of cells. The process is critical of the normal growth and development of complex organisms, including humans. For example, development of branch structures, such as lungs or fingers begin with the development of larger mass and then loss of the material in between the branches. Apoptosis also plays a role in controlling cell growth. So, too little apoptosis can result in over-growth of cells, leading to diseases such as cancer and too high a rate of apoptosis can lead to tissue destruction, such as in the case of neurodegenerative diseases. IGERT student Jennifer Rochira worked with a interdisciplinary and inter-institutional partnership of cell biologists and physicists at the University of Maine and the Maine Medical Center Research Institute, all participants in Umaine’s IGERT-funded Ph.D. In Functional Genomics program. Dr. Rochira (she has now graduated) studied the functioning of a recently discovered peptide called NRAGE which is short for neurotrophin receptor-interacting melanoma-associated antigen protein. NRAGE functions in controlling the apoptotic pathway.

Using a technique called FRET, or fluorescence resonance energy transfer, she was able to demonstrate that the X chromosome-linked inhibitor of apoptosis (XIAP) was found within the cell within 10nm or less from NRAGE, strongly indicating the two proteins interact. Dr. Rochira further showed that a small section of NRAGE, a short sequence of six amino acids that is repeated within the protein was the point of contact between NRAGE and XIAP. She then proceded to show that addition of just the short, 6-amino acid peptide to cells disrupted the apoptotic pathway. More work needs to be done but these results point toward a candidate molecule that could be used to treat disease that arise as a result of errors in the programmed cell death pathway. It is also an example of a successful interdisciplinary collaboration leading to new discoveries and a potential new therapeutic agents for a wide range of diseases.

Address Goals

The described Highlight was part of a research project leading to a successful PhD thesis. The student entered the program with a degree in electrical engineering and working with a cell biologist and a physicist, has learned both the conceptual framework of biological systems and optical physics to enter the workforce capable of moving easily among different disciplines.

The discovery resulting from this research expands our understanding of the fundamental molecular mechanisms that control cell growth, development and death.