Ripped Genes: How a Junior Faculty Fellow Investigates the Nuances of Cells

BY ALEX JOHNSON

Ana Fiszbein has always been interested in biology, but she became fascinated with molecular biology in college after learning about the intricacies of what happens inside of mammalian cells. Now, Fiszbein studies mammalian genes. Genes are incredibly complex structures, but they control and regulate almost everything in the human body. And Fiszbein’s lab studies them using an equally complex research process.

Fiszbein, a Junior Faculty Fellow at the Hariri Institute and Assistant Professor in Biology, is interested in understanding how different regions of the gene are activated, or expressed, and how this affects the gene’s function. A process known as splicing helps create genes with very specific jobs by cutting genetic material at certain points.  How genetic molecules are spliced determines the function of the proteins they create. For example, a gene that produces a protein providing structure to tissues within the body might regulate energy processes within a cell if it were spliced differently.

Fiszbein’s lab focuses on understanding the link between splicing and the job of the gene that is created. “Mammalian genes are very complex,” said Fiszbein. “If you compare mammalian genomes to other species, they have much more DNA [genetic material] but we still don’t understand what all of it is doing.” She published a paper recently that classifies the starting and ending points of genes and describes how the variability of splice sites across even a single gene can change its length and function. “From the same gene, we can make a thousand different proteins because the gene is spliced differently,” explained Fiszbein. “Sometimes these proteins have similar applications, but other times they are totally different.”

The team uses a mix of computational and experimental methods to study gene expression. The two methods complement each other, and can be used interchangeably in the investigation process. At times, she uses computational methods to extract patterns from a large set of data.  These patterns are then used to design experiments.  Other times, experiments yield an unexpected or surprising result, so the data is then put into a computer to analyze additional gene data and test for a pattern.

Fiszbein’s process of using both laboratory experimentation and computer programming is unique and is central to the advancement of molecular biology as the amount of available data continues to grow. “I believe that being able to work with computational tools in biology is extremely important, it’s the future,” she said.

Her lab applies this knowledge to study diseases linked to genetic issues, like breast cancer. Fiszbein’s research can lead to treatments that involve editing where cancer genes start and end so that the resulting proteins do not cause any harm. Her team is made up of people from both biology and computer science backgrounds, and Fiszbein believes in both learning and pulling from other disciplines to help advance genomic research.   “I believe that we need to understand gene expression in cells to combat a suite of diseases,” said Fiszbein. These unique research methods create an adaptable strategy to study big patterns in genetic data, as well as small unexpected outcomes in experiments. This allows Fiszbein’s lab to pivot to big or small nuances, and make real progress.

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