Isabel Esain Garcia awarded PhD Thesis Prize

Dr Isabel Esain Garcia has won this year’s PhD Thesis Prize. This Prize is awarded annually to a student who has undertaken an outstanding research project to the highest standards during the course of their PhD study at the Cancer Research UK Cambridge Institute.

Esain Garcia completed her PhD in the Balasubramanian Group, supervised by Prof Shankar Balasubramanian and Dr David Tannahill. In her doctoral research, Bel discovered a new molecular mechanism in cancer gene regulation opening up a new therapeutic window for cancer treatments.

Research in the Balasubramanian group focuses on exploring how a four-stranded version of DNA is involved in key biological processes, such as gene expression and disease. While most people are familiar with the double helix structure of DNA, there is also a version of the molecule which has a quadruple helix structure. These are known as G-quadruplexes (G4s).

This difference in the 3D structure of DNA molecules can significantly affect how and when genes are turned on and off in cells. The aim of Esain Garcia’s research during her PhD was to target and engineer the DNA structure in human cells to regulate the expression of the MYC gene, which is one of the most critical genes known to control how cancer cells divide.

Using CRISPR, a cutting-edge genome editing tool, alongside other advanced molecular analysis methods, she was able to demonstrate that G4 structures cause MYC gene activation. Her research showed that this effect was specific to the G4 structure itself, because when it was replaced with an unrelated sequence that folded into a similar 3D shape, the original gene expression was recovered.

In the final phase of her PhD research, Esain Garcia investigated a new way to take control of G4 formation in cells to alter the expression of the MYC gene by introducing small chemical modifications to the DNA. Using a chemical process called DNA methylation, she was able to destabilise the folded G4 structures. This led to the precise control of the expression of this cancer-causing gene.

Currently, the effectiveness of cancer therapies can be limited by patient-specific genetic mutations. This research, however, identifies a new way to control the expression of cancer genes by manipulating their physical structure. This insight opens up the possibility of a type of cancer treatment that could be applied universally, regardless of a patient’s genetic signature.

In response to the news, Isabel Esain Garcia said: “I am truly honoured to have been awarded the Cancer Research UK Cambridge Institute Thesis Prize 2024. Knowing that my hard work and results were recognised really means the world to me. I am thankful to the Academic Development team and the selection committee for awarding me this Prize and I would also like to congratulate my fellow colleagues for their outstanding research and discoveries”.

Prof Balasubramanian and Dr Tannahill said, “Isabel is a capable and committed young scientist. Her experimental design, execution and analysis were superb. In turn, the outcomes of her PhD study provide arguably the most compelling data to date to settle a central question (and controversy) in the field, by supporting a causative role for these DNA secondary structures.”

Isabel Esain Garcia has now taken up a position in Nobel Laureate Prof Jennifer Doudna’s laboratory at the University of California, Berkeley. Here she is continuing to develop her expertise in precision genome engineering by investigating new ways to target and edit chromosomes with the aim of identifying new ways to treat complex human disease.