4M euros for research into nuclear metabolism

Part of the preparatory work leading to NUCLEAR has been a four-year journey of discovery into metabolism in the nucleus by Dr Żylicz and his team. A key part of the team’s initial work was the identification of which metabolic players locate to the nucleus. It was already known that metabolites are important in the decision making process of cells but now the question is why are they produced in the nucleus. What is missing is the key observation that is puzzling the field. Metabolism was thought to be taking place in the energy factories of the cells i.e. mitochondria. Now the field has realised that in stem cells and cancer, metabolism also takes place in the nucleus.

Helping sustain cellular homeostasis, which is crucial for cell function, nuclear metabolism and the study of metabolic regulation has yet to be fully understood, but we now know that stem cells and cancer cells have nuclear metabolism.

“We've now found that metabolism regulates decision making processes of cells. We have also performed screens for metabolic regulators that mediate these phenotypes but we haven't yet addressed this big question of nuclear function. We don't know yet what is the specific role which this project will go into depth with,” said Dr Żylicz.

This grant will provide the opportunity to further study nuclear metabolism and project NUCLEAR, soon entering the recruitment phase, could result in the design of new drug targets for diseases, such as cancer.The developmental aims before this work can be applied to human disease can be divided into three areas:

• Developing new tools to study metabolism in the nucleus
• Using these tools to understand if nuclear metabolism is regulating the DNA in the nucleus
• Discovering where nuclear metabolism might be playing a role in the development of diseases, such as cancer

This work will be taken forward by a consortium of professionals from across Europe, made up of a network of PhD students and technology developers through to fundamental scientists and pharmaceutical companies, led by Dr Marcus Buschbeck.

The discovery that metabolism regulates the decision making processes of cells has led to the significant question of nuclear function, which this project will focus on answering through the collaboration between scientific investigation and technology.

“What NUCLEAR will allow us to do is take our research to another level. Not only applying what we know but also collaborating with other experts to start to tackle these big questions. In a way it was not possible before due to technological limitations,” said Dr Żylicz.

Dr Żylicz and his team found through their research that metabolism regulates the first lineage decision process in cell development. This means that the first decision a cell makes after fertilisation is metabolically regulated.

​​The next step, and what the consortium will work together on, is moving from observation of these cell and stem cell characteristics to understanding why they behave as they do, a question that technology will play a huge part in answering.

“I think we're now, for the first time, going beyond description, and really attacking the function and the biological relevance and role of these phenomena. I think the whole technology development and applying it to human disease could really open up new avenues for disease modelling and understanding, but also hopefully treatment one day,” said Dr Żylicz.

With the collaboration between groups within the consortium, and the fact that technology is at a more advanced level than ever before, this question can be answered and, in time, translated into stem cell and disease treatment technology through project NUCLEAR - metabolic regulation of genome function and cell identity.

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