T H E   N I H   C A T A L Y S T     M A Y  –  J U N E   2005




by Aarthi Ashok

Three hundred twenty students in graduate programs the world over are currently enrolled in the NIH Graduate Partnerships Program (GPP). About 85 percent are U.S. students enrolled in Ph.D. programs and the rest hail from a variety of international universities. Forty-five new students will join the partnership programs next fall. Expanding their research projects in labs at 21 of the NIH institutes, GPP students have access here to specialized resources that enable them to ask—and perhaps answer—more complex questions than otherwise possible in their universities, says Richard McGee, director of GPP Student Affairs, who opened the Second Annual Graduate Student Research Symposium, held April 22.

In oral and poster presentations, the research of 66 graduate students was showcased. Below are two examples of the presented thesis work done at NIH. The coveted Outstanding Mentor Award, selected from among nominations by the graduate students, went to NIDA’s Toni Shippenberg, integrative neuroscience chief, who was named by student Raf Schepers.

David Culp

Proteomic analysis of mouse melanoma tumor progression: a study to identify proteins associated with tumor immune evasion
W. David Culp, Jr., Protein Biochemistry Section, NEI, and Cancer Centrum Karolinska, Karolinska Institute, Sweden

David Culp wanted to understand how tumor cells evade the immune system and decided to examine changes in protein expression in solid tumors during the growth of the tumor in vivo.

He was intrigued by a previous finding that showed that when a mouse was challenged with a melanoma and given a vaccine three days later to kill the tumor, the mouse successfully eliminated the tumor cells and was able to survive. However, if the vaccine was delayed to seven days after the initial challenge, then the mouse was not able to eliminate the cancer cells and succumbed to the tumor. He therefore decided to look for protein expression differences between a day-3 and a day-7 tumor.

Culp and his colleagues used 2-D–gel electrophoresis and subsequent mass spectrometric analysis to identify any proteins that were altered in expression between the day-3 and day-7 tumors in the B16-F10 mouse model of highly metastatic melanoma. They identified 29 proteins (P <0.01) with a 1.6 to 5.6-fold change in expression and 92 proteins (P <0.05) with 1.6 to 19.3-fold change in expression. The highest number of changes occurred between day 5 and day 7 of tumor progression. Translationally controlled tumor protein, which is known to be associated with cell growth, is dramatically upregulated in their system, and such proteins will now be their focus. Culp sees using RNAi to knock down expression of such proteins as a potential antitumor treatment strategy.

A Catalog for the transcripts from the venomous structures of the caterpillar Lonomia obliqua: Identification of the proteins potentially involved in the coagulation disorder and hemorrhagic syndrome
Ana da Veiga, Laboratory of Malaria and Vector Research, NIAID, and Universidade Federal do Rio Grande do Sol, Porto Alegre, Brazil

Ana da Veiga and mentor Ivo Francischetti

The caterpillar Lonomia obliqua is covered with spiny bristles that deliver venom to anybody who might happen to brush against it in Southern Brazil. The venom-induced hemorrhagic syndrome and coagulation disorder are severe and in extreme cases can cause kidney failure and death.

Ana Veiga sought to explore the molecular mechanisms by which this venom induces these severe symptoms. She and her colleagues used SDS-PAGE to separate out the proteins present in the venomous structures of the caterpillar and Edman degradation to obtain the sequence of these proteins. They also constructed cDNA libraries to generate a transcriptome—a catalog of L. obliqua cDNAs that encode proteins involved in venom induction.

Analysis of the protein families found in the transcriptome showed that several proteins with toxic functions, such as serine proteases, serpins, and lectins, were all present in the bristles of L. obliqua. Veiga has also been able to characterize cDNAs that encode for a prothrombin activator–like protein and for a fibrinogenase. The group’s current hypothesis, she said, is that the prothrombin activator–like protein and the fibrinolytic protein are two venom constituents responsible for severe hemorrhagic syndrome and that many other molecules identified in the study may also play a role in venom production and release.

Ed. note: This sample of the work done by two GPP students is a prelude to future articles that will feature innovative research by graduate students at NIH.


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