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April 18, 2005

Biologist Melissa Jurica earns prestigious grant from Searle Scholars Program

By Tim Stephens

The Searle Scholars Program has awarded Melissa Jurica, assistant professor of molecular, cell, and developmental biology, a three-year, $240,000 grant to support her research. Jurica, who studies the complex system by which human cells process genetic information, is one of just 15 young scientists awarded the prestigious grants this year.

Melissa Jurica

Melissa Jurica's research focuses on a tiny molecular machine known as the spliceosome.

The Searle Scholars Program makes grants to selected universities and research centers to support the independent research of exceptional young faculty in the biomedical sciences.

This is the first year that UCSC has been invited to participate in the program. Jurica, who joined the UCSC faculty in 2003, is the campus's first Searle Scholar.

Jurica's research focuses on a tiny molecular machine known as the spliceosome, which edits the genetic code before the code gets translated into the protein molecules that carry out a vast range of biological functions.

"It's like when you shoot a movie and you don't need all the footage, you cut some parts out and splice together the parts you want. That's what the spliceosome does with gene sequences," Jurica said.

Most people are familiar with the idea of genes as DNA sequences in the chromosomes. The genetic information in a gene is encoded in the sequence of chemical building blocks (As, Cs, Gs, and Ts) in the linear DNA molecule. When a gene is active, its DNA sequence gets copied into an RNA messenger, but the information there isn't actually ready to be used--it needs to be edited before it can direct the synthesis of proteins.

"RNA splicing is absolutely necessary for gene expression, and there are cancers and other diseases associated with problems in splicing," Jurica said.

In some cases, the same gene sequence can be edited in different ways, so that one gene can produce a variety of different protein molecules. This phenomenon, known as "alternative splicing," is especially common in humans. It is the primary explanation for the surprisingly small number of genes scientists have been able to identify in the complete human genome sequence.

The spliceosome is the key to understanding how the body's cells control the process of alternative splicing to ensure that the right protein gets made at the right place and time. But the spliceosome is extraordinarily complex and difficult to study. It is composed of more than 100 different proteins and several different RNA molecules that come together to form a highly dynamic and complicated structure.

The assembled spliceosome is about one millionth of an inch in diameter. Jurica is using several techniques to study the structure of the spliceosome, including electron microscopy and x-ray crystallography. She is also using biochemical techniques to investigate how the spliceosome is assembled from smaller components and how it carries out its functions.

Jurica is affiliated with UCSC's Center for Molecular Biology of RNA, where she is able to consult and collaborate with scientists involved in similar research. For example, Manuel Ares, professor of molecular, cell, and developmental biology, studies RNA splicing in yeast, focusing in part on the effects of mutations and environmental changes on the regulation of alternative splicing. Harry Noller, Sinsheimer Professor of Molecular Biology and director of the RNA Center, has used x-ray crystallography to determine the structure of the ribosome, another complex molecular machine, which carries out protein synthesis.

"The collaborative environment of the RNA Center makes it a good place to do structural biology on the spliceosome. There are great structural biologists and splicing experts here," Jurica said.

The Searle Scholars Program was established at the Chicago Community Trust in 1980. It is funded from the estates of Mr. and Mrs. John G. Searle. Mr. Searle was the grandson of the founder of the pharmaceutical company G. D. Searle & Company. It was Mr. Searle's wish that certain funds be used to support research in medicine, chemistry, and biology. To achieve this goal, grants are made to selected academic institutions to support the independent research of outstanding individuals who are in the first or second year of their first appointment at the assistant professor level, and whose current appointment is a tenure-track position.

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