King's College London

Professor Ruepp’s lecture drew a large crowd of colleagues, friends, family and members of the public. The event commenced with Professor Cathryn Lewis welcoming guests and introducing Professor Ruepp, emphasising the enormous amount of work it takes to achieve this milestone in an academic career.

“You’ve convinced many people of what you’ve achieved. This needs to be celebrated and that’s exactly what we’re doing here this evening,” said Professor Lewis in her introduction.

Professor Ruepp then took to the podium to share how he came from a small village in Switzerland to leading a successful research group in London. He described with humour and sincerity how he took an unconventional initial path, focusing his studies on Latin, before pivoting into biochemistry and discovering his love of RNA biology at the University of Bern.

An ‘exception to the rule’

He took the audience with him along his journey, through his initial interest in eukaryotic gene expression — the mechanism by which genes are read out into the proteins that govern the function of every cell in our bodies — to his realisation that a molecule called mRNA was his real passion.

mRNA can be viewed as the middle step in the process of gene expression; it contains a blueprint from which proteins are made. Crucially, as Professor Ruepp explained in his lecture, it presents a major opportunity for cells to regulate which genes will be expressed, which won’t and which form of the protein will be made.

His interest was piqued by the way cells process the ends of messenger RNAs. Most mRNAs receive a poly(A) tail, but as an undergraduate he became fascinated by the unusual exception of replication-dependent histone mRNAs, which are processed in a different way. Understanding this process has helped pave the way for modern RNA-based therapies.

From mRNA to ALS

Serendipitously, through his research into mRNA processing and regulation, Professor Ruepp started to be interested in a protein called FUS — an RNA-binding protein present in every cell in the body. Around the time that Professor Ruepp started to be interested in FUS, Professor Chris Shaw and Dr Caroline Vance at King’s discovered that mutations in FUS genes cause ALS.

FUS became the focus of his postdoctoral research. Professor Ruepp quickly realised that to understand what FUS does inside cells in both people with and without ALS, that looking at human motor neurons would be essential.

A lifelong love of mountains

The mountains have always been important to Professor Ruepp and featured in several unexpected anecdotes. While seeking independent funding, he met Georg Heinrich Thyssen-Bornemisza, who established the NOMIS Foundation, in the Swiss mountains and explained his plan to create ALS disease models by converting stem cells into motor neurons carrying FUS mutations. The foundation subsequently funded the project, laying the groundwork for his independent research career.

Mountains cropped up again unexpectedly when Professor Ruepp was applying to be part of the UK Dementia Research Institute at King’s College London. When he found out that his interview to be a group leader would fall during a planned hiking trip, rather than cancelling the trip, he paused the trip to meet Professor Chris Shaw at King’s for his interview, before returning to the mountains to finish the climb.

A scientific home

At King’s, Professor Ruepp described finding his scientific home, surrounded by like-minded researchers, passionate about RNA biology and developing treatments for ALS. He immediately was surrounded by a community that supported him and inspired his research, sharing an office with fellow ALS researcher Dr Caroline Vance and collaborating closely with Professor Chris Shaw and Dr Sarah Mizielinska. Now his research team of 15 scientists work across the full spectrum from fundamental science to therapeutic discovery research.

The event concluded with his close collaborator Dr Sarah Mizielinska giving the vote of thanks.

“Your drive and creativity have brought your career to this point,” she said addressing Professor Ruepp. “Some of us who have worked with him have seen him speak and write about working from bench to bedside. For him, these for him are not just words. These are active commitments. He takes fundamental RNA biology mechanisms to potential therapeutics both for motor neuron disease and across dementia.”