Kristoffer Vitting-Seerup

Project title

Beyond Genes: The Atlas of Causal Isoform Regulation

What is your project about?

All humans share nearly identical DNA, yet the activity of our genes determines whether a cell becomes a brain cell, a muscle cell, or a cancer cell. Each gene can produce several versions of a protein, called isoforms, with very different functions.      

Unfortunately, isoforms are often overlooked in modern research and drug development. Our studies show that roughly half of all biological changes occur through isoforms, meaning that much of current biomedical research is missing the full picture.      

This project aims to change that. We will create the first map of how human genes and isoforms regulate one another – an "atlas" of these relationships in our cells. With this atlas, we can do something entirely new: trace diseases back to the central genes that control them.    

These regulators are obvious candidates for new drugs, since altering their activity can halt an entire disease program at its source. We will use this approach to analyse thousands of both common and rare diseases, many of which currently lack effective treatment.     

The result will be a resource made available to researchers worldwide and a foundation for more precise, isoform-aware drug development.

How did you become interested in your particular field of research?

My interest in isoforms arose somewhat by chance. During my master's thesis, I worked with a dataset where I quickly answered the original research question. To make use of the remaining time, we began exploring other possibilities in the data. At that point it had just become feasible to analyse isoforms at scale, and we decided to investigate what could be learned from this previously overlooked part of biology. It soon became clear that isoforms hold far more biological information than most researchers assumed. Since then I have been fascinated by their importance for gene regulation, disease, and treatment, and I have dedicated my research to developing the methods and resources needed to make isoform analysis a natural part of biomedical research.

What are the scientific challenges and perspectives in your project?

The project's main research challenge is that most of today's biological and medical research treats genes as a single unit, even though each gene can produce several different protein variants, called isoforms, with widely differing functions. Our research shows that roughly half of all biological changes occur through isoforms. When isoforms are ignored, a large part of the mechanisms that govern cell function and contribute to disease is therefore missed. This limits both our biological understanding and our ability to identify new targets for treatment.

What is your estimate of the impact, which your project may have to society in the long term?

The same gene can produce several different protein variants – isoforms – and it is often these variants that determine whether a cell functions normally or develops disease. How genes and their variants regulate one another across the body, we have so far known only in fragments.    

We can now investigate this for the first time. Three things are falling into place at once: new analytical methods from my research group, vast amounts of publicly available data, and modern methods for uncovering cause and effect rather than mere correlation.

Together they let us build the first atlas of causal relationships between genes and isoforms in humans – a map that pinpoints the central regulators behind biological processes and diseases. At the same time, we are conducting the first large-scale analysis of isoforms at single-cell resolution.      

The atlas will become a resource for researchers worldwide and can point to new treatment targets across thousands of common and rare diseases – including many for which no effective treatments exist today. In the longer term, it can pave the way for more precise drugs and strengthen a broader shift towards an isoform-focused understanding of biology and disease.

Which impact do you expect the Sapere Aude programme will have on your career as a researcher?

Sapere Aude will strengthen my development as an independent research leader. The grant gives me the opportunity to pursue a more ambitious, long-term research direction than day-to-day operations would otherwise allow, and to build and train a team around a coherent vision rather than isolated projects.    

As a research leader, the grant will strengthen my ability to recruit and mentor junior researchers, communicate a shared vision, and lead a team towards common goals – thereby developing the managerial tools required of a research leader.