27 June 2019

Large EU grant for training the next generation of protein researchers

Proteins

The Novo Nordisk Foundation Center for Protein Research is getting DKK 33.5m from ’The Innovative Training Network’ for training PhD researchers. The grant will increase insights into special control enzymes that maintain the protein balance in human cells.

The new PhD researchers will uncover the protein codes 'SLiMs' (in red), which in the picture are bound to another protein (in gray).

The Novo Nordisk Foundation Center for Protein Research (CPR) at the University of Copenhagen is getting DKK 33.5m for a new training programme for PhD researchers who will be exploring unresearched parts of the human protein composition in the future, also called the ’proteome’.

The grant has been awarded by EU’s Marie Skłodowska-Curie’s ”Innovative Training Network’ to 11 collaborative partners, including international universities and companies in the life science industry. In the first instance, the award will be used to appoint two PhD researchers at CPR. Prof Jakob Nilsson, CPR, was responsible for the application process.

Code breakers to explore unknown territory
The body has more than 20,000 known proteins, which serve as the body's building blocks by contributing to its structure and maintenance. They also play a crucial role in the development of a whole range of diseases, including DNA-damage diseases such as cancer, diabetes and neurodegenerative conditions. This is why researchers at the Novo Nordisk Foundation Center for Protein Research have had been studying the proteome in-depth over the past ten years to map the function of proteins and their interaction in the body.

The results show that they have only identified about half of proteins' functions. This is due to the fact that it is very difficult to analyse the outstanding half, which consists of so called intrinsically disordered regions. Research have shown that these intrinsically disordered regions contain vast quantities of important “protein codes” that determines how proteins bind to each other, how they behave and undertake their functions in the body.

New technology has made it possible to systematically identify these protein codes (also known as SLiMs - short linear interaction motifs), and researchers expect the proteome to contain between 100,000 and 1 million of these codes. The new grant will be used to train a new team of protein researchers to identify the SLiMs, ”crack” the information codes and analyse how it will be possible in time to regulate protein function.

”To put it more simply, these protein structures are rather like bits of spaghetti, containing important information that controls protein functionality. By painstakingly identifying and analysing SLiMs, we can construct the interaction codes for proteins function. So the new researchers can look forward to incredibly exciting and important pioneering work on the proteome”, says Prof Jakob Nilsson, Novo Nordisk Foundation Center for Protein Research.

Control proteins with great medicinal potential
In the first instance, the project will be focusing on a special group of enzymes that attaches and removes a small label or tag called ubiquitin. This is important for controlling the protein balance in the body’s cells since ubiquitin then escorts the marked protein to destruction. These enzymes especially use ’SLiMs’ to recognise and tag proteins in the cell for destruction. Researchers hope that cracking their SLiM codes will make it possible in time to regulate the quantity of proteins in cells that can lead to various diseases.

Over the next four years, the researchers will be comparing the approximately 1000 ubiquitin enzymes in the body with the enormous volumes of protein code to work out how the codes can be used to produce new drug targets.

Ubiquitin-tagging of cellular proteins via so-called ’PROTACS’ (PROteolysis-TArgeting Chimeras) has attracted great attention in the life science industry and so the PhD researchers will be in working with pharma companies GSK (GlaxoSmithKline) and Beactica to exploit the potential of their discoveries.

Close international collaboration to map the proteome
Researchers have cracked the body's genetic code (DNA) in recent decades and now the 11 collaborative partners in the project are making a start on further clarification of the proteome's code.

The PhD researchers will be working closely and have placements with international universities and life science companies to exchange data and experience which could have a major impact on the further work done by the Center on the body's unresearched territories.

The two PhD researchers will be employed in the Nilsson Group and Mailand Group at the Novo Nordisk Foundation Center for Protein Research.

Read more about the EU Commission's Marie Skłodowska-Curie ”Innovative Training Network here: https://ec.europa.eu/research/mariecurieactions/actions/get-funding/innovative-training-networks_en

Contact points

Professor Jakob Nilsson
Novo Nordisk Foundation Center for Protein Research
E: jakob.nilsson@cpr.ku.dk
T: (+45) 3532 5053
https://www.cpr.ku.dk/consortia/ubimotif/ 

Communication Adviser Andreas Westergaard
Faculty of Health and Medical Sciences
E: andreas.westergaard@sund.ku.dk
T: (+45) 5359 3280