TU Delft and LUMC explore new avenues in RNA biology

Last year’s discovery of sugar-coated RNA – a macro-molecule much like DNA but essential for regulating many cellular processes – has opened up a whole new area of cell biology. A collaboration between TU Delft and LUMC sets out to unravel the role of this molecule in stress-associated disorders. 

Chirlmin Joo, associate professor within the department of bionanoscience at TU Delft, has always been fascinated by how nano-machines work. ‘There are so many beautiful nano-machines inside cells,’ he says. ‘For many of these machines, we still don’t know how they work or what their exact function is.’ Many others may still need to be discovered - or recognized. It took a new point of view, by researchers from University of California-Berkeley, to even detect the so-called glycoRNA (sugar-coated RNA).

There are so many beautiful nano-machines inside cells.

Chirlmin Joo, Associate Professor, Department of Bionanoscience at TU Delft

Sugar and stress

Now that the existence of sugar-coated RNA is known, it raises all sorts of questions. Joo: ‘Using my expertise in biochemistry and single molecule biophysics, I can answer questions about how it works and how it interacts with other proteins. But I cannot address how it is generated and what it does inside the cell.’ This is where Vered Raz comes in, associate professor in human genetics at LUMC. She has vast experience with both RNA and the role of complex sugar aggregates in the cell, but the combination of the two is new to her as well. She came up with the hypothesis that sugar-coated RNA may play a role in age-associated stress. Also adding vital expertise to the project is Thomas Sharp, from the department of Cell and Chemical Biology at LUMC, who will investigate its exact structure.

Our combined expertise allows us to unravel the mystery surrounding glycoRNA.

Discovery phase

As so little is yet known about sugar-coated RNA, the research being performed is very much in the initial discovery phase. LUMC will grow cells that are a model system for ageing. RNA will be extracted at different stages of the cell cycle after which detailed biochemical analysis is performed at TU Delft. It will provide information about the exact structure of both the sugar part and the RNA part as well as to how they are connected. ‘We can then go back to the cell-system to validate our findings or use the expertise of my group to make movies of how these single molecules interact with each other,’ Joo says. ‘Using our combined biochemical, biophysical, structural biology, and human genetics expertise, I believe we have a unique opportunity to unravel the mystery surrounding sugar-coated RNA.’

Research into glycoRNA is very much in the discovery phase.

Blue sky thinking

The two years that a postdoc will spend on the project is too little time to even come close to any real-life applications. But, by then, the researchers hope to have established a consortium of a number of research groups, including expertise on live cell imaging and proteomics, enlarging the scope of the questions that can be addressed. In the long term, such a consortium may discover sugar-coated RNA to regulate the cellular metabolism, opening up a path towards new medicines. Or, if not regulatory, it may reflect the state of the cell, leading to new diagnostic tools. And, perhaps, it takes some new method of analysis to completely unravel the role of sugar-coated RNA. Joo: ‘As a biophysicist, developing such a completely new tool certainly is one of my ambitions.’

In the long run, our research may lead to new medicines or new diagnostics.