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Fleming fellow to study key DNA copying process

Francisco Bastos de Oliveira, a researcher at Cornell studying a novel cellular pathway during replication that may one day lead to better cancer drugs, was awarded the 2010 Sam and Nancy Fleming Research Fellowship from Cornell's Weill Institute for Cell and Molecular Biology.

Bastos de Oliveira, a postdoctoral researcher in the lab of Marcus Smolka, assistant professor of molecular biology and genetics in the Weill Institute, is Cornell's third Fleming fellow, following Duane Hoch (2009) and Jason MacGurn (2008).

Each fall, the three-year fellowship is given to a postdoctoral researcher at Cornell's Ithaca campus who received his/her Ph.D. within two years of the application deadline and is nominated by his/her lab's principal investigator. The candidate's research should align with the Weill Institute's focus on answering big yet basic questions in cell biology; ideally, the research should bridge across departments on Cornell's Ithaca campus and with Weill Cornell Medical College.

"We are looking for people who are really taking on a bigger question, a riskier project, people who are looking for the gold," said Scott Emr, director of the Weill Institute. "The Fleming fellowship program has allowed us to recruit extremely talented young scientists to Cornell who are doing cutting-edge research in basic biomedical sciences," he added.

Bastos de Oliveira's work revolves around understanding a unique pathway that occurs when damaged DNA disrupts the cell's replication machinery. Replication is a fundamental process occurring in all living organisms to copy their DNA.

In such instances, a protein named Rad53 becomes activated and spreads throughout the cell's nucleus, signaling that the replication machinery is blocked by damaged DNA. Through a complex set of protein interactions, Rad53 indirectly facilitates the cell to increase the synthesis of nucleotides (also known as dNTP), the building blocks of DNA. These nucleotides are then employed by the cell's replication machinery for moving forward.

"We are proposing a new pathway regulated by Rad53 to maintain proper levels of dNTP during replication stress," said Bastos de Oliveira.

Bastos de Oliveira and Smolka discovered evidence that this process, while less accurate, keeps the replication machinery moving forward. When a lesion occurs in DNA, part of the code to be copied is missing. In order to continue copying, the cell's replication machinery replaces the missing code with spare nucleotides, which are now available thanks to Rad53. Though the exact code is lost, the copying process can continue in this way.

"In the end, it lets the cells survive at the expense of mutations," said Smolka.

The researchers hope that new drugs that target this pathway in cancer cells may inactivate the process and create genomic instability and cell death. Also, many chemotherapy drugs create replication stress in normal cells as well, so by understanding this pathway, the hope is that new drugs may allow normal cells to survive while killing cancerous ones.

The fellowship was established in 2008 through a gift from Sam Fleming '62, BChemE '63, chairman of Cornell's Life Sciences Advisory Board, a member of the Weill Cornell Board of Overseers, a presidential councillor, and former vice chairman of the Cornell Board of Trustees, along with his wife, Nancy. The Flemings actively support the New Life Sciences Initiative, the Weill Cornell Medical College (WCMC) and other important areas on Cornell's Ithaca campus.

In an effort to foster collaborations between Cornell's Ithaca campus and WCMC, the Flemings support the Research Scholar Award in Intercampus Collaborations, which recently announced its first Nancy M. and Samuel C. Fleming Research Scholar in Intercampus Collaborations, Henning Voss, associate professor of physics in radiology at WCMC, who will be collaborating with Chris Schaffer, assistant professor of biomedical engineering at the Ithaca campus.

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