The Pew Charitable Trusts has named Angela Brooks, assistant professor of biomolecular engineering at UC Santa Cruz, a Pew Scholar in the Biomedical Sciences. Brooks will receive a $300,000 award over four years to support her research on how mutations associated with cancer cause changes in gene expression.
The Pew Scholars Program in the Biomedical Sciences provides funding to young investigators of outstanding promise in science relevant to the advancement of human health. The program makes grants to selected academic institutions to support the independent research of outstanding individuals who are in the first few years of their appointment at the assistant professor level.
Brooks is an expert in the analysis of RNA sequencing data and is especially interested in the role of RNA splicing in gene expression. When a gene is expressed, its DNA sequence is copied from the chromosome to an RNA molecule, which then undergoes splicing to remove parts of the sequence. Only then can the RNA perform its function and direct the production of a protein. Splicing is governed by a complex regulatory system, and most genes can be spliced in different ways to produce different versions of a protein.
Mutations in the genes that regulate splicing are common in cancer cells. A gene called U2AF1, for example, is mutated in multiple types of cancer, including lung cancer. In previous research, Brooks showed that mutations in this gene lead to aberrant splicing of many RNAs. Now she plans to perform a comprehensive assessment of the effects of U2AF1 mutations, determining the sequences of all RNA transcripts produced by cells with the mutated gene.
"We want to get a complete picture of what is being altered by these mutations," Brooks said.
This effort will involve a suite of advanced methods, including nanopore sequencing technology pioneered at UC Santa Cruz. "I was excited to come to UC Santa Cruz in the first place because of the expertise here in nanopore sequencing technology," Brooks said. "There's a great community of researchers here that I can collaborate with."
Nanopore sequencing has several advantages over traditional sequencing technologies, including the ability to directly sequence an entire RNA transcript without chopping it up into smaller segments or making a DNA copy of it. The "long-read" sequences possible with nanopore sequencing will enable Brooks to directly assess the RNA output of the cells.
"We will assess whether alternatively spliced RNA transcripts continue to direct the synthesis of proteins and what effect these RNAs have on the activity of genetic and cellular pathways," she said. "These findings will advance our understanding of how changes in RNA processing affect cell function and could lead to novel approaches for treating diseases, including cancers, in which splicing is abnormal."
Much of this work will involve building the computational tools needed to analyze the data from direct nanopore sequencing of RNA transcripts extracted from cells. The tools Brooks develops will have applications in a wide range of research, but she said it is important to develop them in the context of a specific project.
"Rather than building a hammer and then looking for a nail, I like to couple the tool building with a biological question we're trying to answer. You can build a better tool that way," she said.
