New IBEC group creates ‘fitness heatmaps’ of gene mutations

The start of the autumn semester finds a new face in IBEC’s research community, with Dr. Benedetta Bolognesi joining the institute as junior group leader.

Benedetta has come from Barcelona’s Centre for Genomic Regulation, where she was a postdoc in Ben Lehner’s and Gian Gaetano Tartaglia’s groups. At IBEC she will launch and lead the Protein Phase Transitions in Health and Disease group.

During her postdoc, Benedetta focused on why certain genes are toxic when over-expressed. She found that, in some cases, they cause toxicity because the proteins they code for end up forming a different liquid phase in the cytoplasm.

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“Proteins that aggregate into solid amyloids, or fibrils, are associated with a number of neurodegenerative conditions, but we now also know that proteins that are toxic can form liquid aggregates as well,” she says.

Her group at IBEC will develop and expand on a method known as deep mutational scanning, which quantifies thousands of both good and bad protein mutations at once to produce a ‘fitness heatmap’. “With deep mutational scanning, we can ‘map’ thousands of mutations in prion-like protein domains and then play with the concentrations and combinations to see which have an impact on health,” Benedetta says. “This high-throughput method will help us uncover how and in what circumstances mutations can result in devastating conditions such as Alzheimer’s or Amyotrophic Lateral Sclerosis.”

Benedetta’s interest in protein aggregates began when she was doing her PhD at Cambridge with Prof. Chris Dobson, founder of the Cambridge Centre for Misfolding Diseases, who was knighted this year. At that time, she was looking at amyloids in relation to Alzheimer’s disease. “After my PhD I wanted to address more general questions, so at the CRG I was able to work with both computational models and yeast with an interdisciplinary fellowship across two labs,” she says. “That got me interested in how protein sequence determines the formation of liquid versus solid aggregates, and what this means for health and disease.”

At IBEC she shares a mission to understand neurodegenerative disease with the nearby Molecular and Cellular Neurobiotechnology group led by José Antonio del Río, and hopes to collaborate with many other groups – and is already familiar with some of them. “In fact, I was at Pavia University at the same time as Lorenzo Albertazzi,” she says. “I’d like to work with him and Pau for their STORM and AFM imaging capabilities, and I’m interested in talking to groups working with mammalian or stem cells with a view to doing tests in more complex models than yeast.”

A mother-of-one, Benedetta likes to get out into the mountains when she’s not doing science, and is delighted to be at IBEC both for its interdisciplinary environment and equipment and for the fact that Barcelona is “a fantastic hub for biomedical science”.