10. maj 2019

Novo Nordisk Foundation is focusing on biological research

Investigator Grant

The Novo Nordisk Foundation has again invested several million in biological research at the Department of Biology. This time, five prominent research leaders each receives the attractive Investigator grant, allowing them to continue and deepen their research areas. It is research that covers a wide range of biology - from DNA and RNA to sustainable crops, diabetes and obesity research.

Biological research is in focus to solve the world´s health problems and to find sustainable solutions for a number of societal problems, including climate change. The Department of Biology at the University of Copenhagen covers a wide range of biology subject areas - from the molecular biology basic research to research within plants, animals and climate.  

Postdoctoral fellow Jakob G. Knudsen receives 10 mDKK (Excellence Emerging Investigator)
Project title: 'Metabolic specialisation of α-cells: In search of pathways causal to hyperglucagonemia'
Type 2 diabetes (T2D) affects more than 400 million people worldwide. Despite great efforts, we have so far been unable to curb the increasing prevalence. While insulin resistance and lack of insulin secretion seems to be the major cause of T2D, it has become clear that the hormone glucagon also plays a critical role. Glucagon is normally secreted to increase plasma glucose levels during fasting but in T2D, glucagon suddenly appears at higher plasma glucose levels and causes hyperglycemia. In this project, Jakob Knudsen will advance single cell resolution microscopy and genetically modify models to determine how
α-cell metabolism and glucagon secretion changes in response to metabolic challenges.

- 'This way we can explore the mechanisms underlying glucagon secretion in T2D. The understanding of α­-cell metabolism and the basic mechanism of glucagon secretion will not only benefit diabetes research, but also lead to new possible treatments for T2D', says Jakob G. Knudsen.

Postdoc fellow Jakob Knudsen

Professor Michael Lisby receives 10 mDKK (Distinguished Investigator) 
Project title: 'Functional characterization of the ZGRF1 DNA repair helicase and its potential as a therapeutic target''.
The research group of professor Michael Lisby studies the mechanisms in the cell that are responsible of repairing damage to its genetic material, the DNA.

- ‘It is well-known that a failure to repair DNA damage can lead to genetic mutation, gene deletions and gross chromosomal rearrangements, which have been linked to a number of immunological disorders, infertility, neurodevelopmental defects, premature ageing syndromes and predisposition to cancer’, explains Michael Lisby.

With the grant from the Novo Nordisk Foundation, the Lisby group will study the function and regulation of a previously uncharacterized human helicase, ZGRF1, in genome stability maintenance and its implications for human health and disease to uncover its potential as a therapeutic target in genome instability disorders.

Professor Michael Lisby

Associate professor Kim Furbo Rewitz receives 10 mDKK (Ascending Investigator)
Project title: 'Identification of signals secreted by the gut that regulate food intake and metabolism'.
The epidemics of diabetes and obesity are one of the major global health challenges. Some of the most promising approaches to treat diabetes and obesity involve manipulation of hormonal signals from the gastrointestinal tract. The gut talks to the brain and other organs, releasing hormones into the blood, that informs us how hungry we are, what we should or should not to eat, and whether the body should store or burn energy. Although some important gut hormones are known,more than 2,000 proteins with potential hormonal function exist,representing a significant unexploited resource for the discovery of new therapeutic interventions for the treatment of metabolic disorders.The aim of this project is to systematically identify the hormones used by the gut to communicate with the brain and other tissues to regulate appetite and metabolism. Identification of gut hormones that regulates hunger and energy storage, may provide new treatments for diabetes and obesity.

Associate professor Kim Rewitz

Associate professor Peter Brodersen receives 10 mDKK  (Hallas-Møller Ascending Investigators)
Project title: 'Mechanistic basis of post-transcriptional gene regulation via N6-methyladenosine-modified messenger RNA'.
The grant allows Peter Brodersen´s group to pursue the research into how a newly discovered mechanism of gene regulation really works, and how it shapes plant growth and development. The study of gene regulation is central to biology, because it explains why cells within an organism acquire very different properties despite the fact that they contain the same genes.

- '‘When a gene is active, it is first copied into so-called mRNA that is the direct template for production of proteins, the workhorses that actually give cells their properties. mRNA can be chemically modified, and such modifications have a crucial impact on mRNA function as templates for protein production’, says Peter Brodersen.

This modification-system is deeply conserved: the same enzyme modifies mRNA in plants and animals, and closely related factors read the modification code. In this project, we will find out how these deeply conserved readers of RNA modifications work: how they help cells grow, divide and mature, and how their regulatory functions relate to other systems of mRNA control.

Associate professor Peter Brodersen

Professor Morten Petersen receives 10 mDKK (Distinguished Investigator)
Project title: 'Exploiting microbial effector targets to optimize plant protection and crop yield'.
Plant diseases and environmental impacts cause every year a serious loss of crops all over the world. This project ' can contribute to create sustainable solutions.
Plant pathogens deliver effector proteins into plant host cells to increase infectivity by modifying or removing protective host proteins. Plants detect effector proteins via NLR immune receptors which monitor host effector targets. In response to effector target tampering, NLRs potentiate immunity. The guard hypothesis thus proposes that NLRs ‘guard’ host ‘guardees’. A corollary to this is that autoimmunity in plants may be due to inappropriate NLR activation and not caused by mutations in negative regulators of immunity as described in many highly cited research papers.

This research will therefore developed a novel, rapid suppressor screen based on specific Dominant Negative (DN-NLR) mutations in a conserved NLR domain. This screen confirmed that autoimmunity in many mutants require NLRs.

- Morten Petersen: 'Since we can now remove the effects of the triggered NLR guard(s), we can properly ask three important questions:
1 – What are the true functions of the guardee proteins?
2 – Why are they guarded?
3 – How can we exploit them to increase plant production?'

Professor Morten Petersen