During my PhD and postdoctoral research, I studied how regulatory elements affect RNA splicing, an important biological process in gene expression. I co-developed a technique called CLIP, which identifies where proteins bind to RNA, and combined it with experimental and computational methods to better understand the splicing process.
Find out more about Jernej and Ben's work
During my initial secondment at the Crick, I worked closely with Nick Luscombe to further develop the experimental and computational approaches that allowed us to examine RNA-protein and RNA-RNA interactions with increasing resolution and scale. This enabled us to study the functions of protein-RNA complexes in the nervous system and roles in neurodegenerative diseases such as ALS and frontotemporal dementia.
We also developed long-term collaborations with several other teams in the Crick, often through joint students such as Oscar Wilkins. Oscar worked with Pietro Fratta’s team to control gene expression by modifying the RNA splicing process.
This opened up additional research directions that inspired our joint projects with Ben and his team.
As a graduate student and postdoctoral fellow, I investigated mechanisms underlying the assembly, regulation and nuclear organisation of splicing complexes.
In my own group, we have developed and applied approaches for the global-scale discovery and characterisation of splicing regulation in diverse contexts. These studies have provided insights into the complexity, mechanisms, functions and evolution of alternative splicing.
Our research has further revealed pivotal roles for alternative splicing in the control of stem cell pluripotency and neurogenesis, and evidence that its dysregulation represents a convergent mechanism underlying autism spectrum disorder.
This latter work has served as a basis for new research we are performing in close collaboration with Jernej and others at the Crick.
I earned my BSc in Molecular Biology from the University of Ljubljana in 1999 and completed a PhD in Molecular Neuroscience at Rockefeller University in 2004. In 2006, I initially established my research group at the MRC Laboratory of Molecular Biology in Cambridge.
In 2013, my research group moved to University College London and in 2016, on secondment, to the Crick.
In 2022, I was appointed Centre Director of the UK Dementia Research Institute at King's College London, and most of the research group is now located at King’s, while a satellite team remains at the Crick.
I received a BSc (hons) in Microbiology at Imperial College London in 1988, and a PhD in Biochemistry in 1991 from the University of London, while working at the European Molecular Biology Laboratory in Heidelberg.
In 1992, I joined the Center for Cancer Research at MIT as a research fellow, and subsequently started my own laboratory at the University of Toronto in 1998. Currently, I am a professor in the Donnelly Centre at the University of Toronto and serve as Director of the University of Toronto’s Donnelly Sequencing Centre.
In 2024, I was appointed part-time Professor of RNA Biology and Genomics at the Centre for Developmental Neurobiology at King’s College London, and joint Satellite Group Leader with Jernej at the Crick earlier this year.
We are attracted by the Crick’s mission to accelerate ambitious, highly collaborative and interdisciplinary research with translational potential. The Crick has enabled the co-location of our and Pietro Fratta’s team such that we can closely collaborate on projects directed at establishing new auto-gated gene therapy strategies for various types of neurological disorders.
This research will be facilitated by daily interactions between our lab members working at the interfaces of molecular systems biology, bioinformatics, machine learning, engineering, neurobiology and disease modelling.
We will also greatly benefit from the Science Technology Platforms available at the Crick, especially the Viral Vector Service Unit, High-Throughput Screening and Robotics, Sequencing, Flow Cytometry, Advanced Imaging, Structural Biology and the Making Lab.
We will be developing and testing new RNA auto-gated vectors that can be used in gene therapy applications to specifically drive therapeutic transgene expression in brain disorder-affected cells, with a focus on autism spectrum disorder and Alzheimer’s disease.
This research forms part of an ambitious eight-year project recently funded by a Wellcome Trust Discovery Award, led by ourselves and Laura Andreae, who is at the Centre for Developmental Neurobiology at King’s.
Our satellite lab will develop the project in close collaboration with Pietro Fratta’s group, who has pioneered gated vectors for ALS.
Currently, we are determining minimal RNA and protein sequence ‘signatures’ that underpin context-dependent regulation of alternative splicing events that are dysregulated in specific diseases. These signatures will then be used as a basis for the design of auto-gated vectors.
We’ve been wonderfully supported by our quadrant lab manager, Martina Pilatova, and by Mike Scopa, Jamie McDermott and others on all the administrative-related tasks. New members have settled in very well this year, and everyone is now busily working together.
It helped that Jernej and some of his lab members were working in the Crick before the start of our joint satellite this year, so all the equipment and reagents were in place for a seamless transition towards addressing the research aims of our joint satellite.
Hard question! I could be a gardener. I’ve done lots of gardening from a young age, learning from my grandparents. I’d love to work with the kind of English gardens that make an impression of there being no gardener.
In a ‘previous life’, I worked in graphic design and illustration and considered going down this path, until one of my biology professors convinced me that I could be an artist in my spare time as a researcher, but not the other way around. He was only partially correct; I do hope to spend more time on drawing one of these days!
