Andrea Quezada

Mapping the structure of Huntington’s brain clumps

People with Huntington’s disease lose control of their bodies and minds. The symptoms are caused by protein clumps in the nerve cells. Supported by a Marie Skłodowska-Curie Individual Fellowship, Andrea Quezada aims to create atomic models of these fibrils at the Max Delbrück Center.

Dr. Andrea Quezada had actually planned to leave research to pursue a career in science administration. But that was before she got hooked on the study of neurodegenerative disorders. The mechanisms behind these illnesses fascinated her just as much as the technologies used to understand how such processes take place in cells.

When Quezada learned that Professor Erich Wanker at the Max Delbrück Center was looking for Marie Skłodowska-Curie Individual Fellowship candidates, she emailed him. A few Zoom meetings later and her project proposal was ready for submission. The European Commission awards the fellowships to support researchers who want to advance their careers in Europe. Her proposal was successful, and since September 1 Quezada has been a scientist in Wanker’s lab.

On the hunt for therapeutic strategies

She will spend two years there researching Huntington’s disease, a currently incurable brain disorder that involves the slow death of nerve cells. “Affected individuals gradually lose their independence, their intellect and their personality,” says Quezada. The disorder is caused by a mutation in the Huntingtin gene which leads to the production of an abnormal protein containing several consecutive glutamines. Glutamine is one of the building blocks of proteins. In Huntington's disease, too many of the glutamine building blocks are forming long polyglutamine chains that gradually clump together and poison nerve cells.

Wanker deciphered these clumps, or fibrils, back in 1997. In the “HUNTING-BrainFibrils” project, Quezada now wants to create atomic models of the fibrils and map the molecular interactions in brain material. “To develop new therapeutic approaches for this cruel disease, we need a detailed understanding of the structure and composition of the fibrils,” she says. Working at the Max Delbrück Center gives her access to technology platforms focused on image data analysis, cryo-electron microscopy and high-throughput proteomics. Another goal of hers is to identify biomarkers that show which therapy is most effective at the different stages of the disease.

Quezada studied chemistry, biophysics and structural biology at the National Autonomous University of Mexico (UNAM). After completing her doctorate, she spent two and a half years in Lisbon doing postdoctoral research. It was during this time that her interest in Huntington’s disease was sparked. Last year, she was involved in a COVID-19 project at the University of Texas in Austin, USA. Quezada believes she will complement well the cell biology expertise in Wanker’s team. “I’m a very curious person,” she says. “While I’m here I hope to specialize in neurodegenerative diseases, and to establish myself as an independent researcher.” Outside the lab she plans to indulge her other passion: flamenco.

Text: Jana Ehrhardt-Joswig


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