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How do genes make us sick with diabetes and obesity?

When we get sick with life style diseases, some kind of gene activity has led to changes in, for example, our metabolism. But which genes? And what are the factors that trigger this altered gene activity?

By Birgitte Svennevig, , 3/7/2022

Science is understanding more and more of human genetics, and there is no longer any doubt that genes play a crucial role when we develop diseases.

- First and foremost, it is important to find out which genes are regulated and which factors regulate them when we get ill: Some can be the key to developing new diagnostic or treatment options. For me, this is one of the big and still open questions in my research, says Jesper Grud Skat Madsen.

But how do you find out which genes are being regulated? And what factors regulate them when we get sick?

The needle in the haystack

According to Jesper Grud Skat Madsen it's like looking for the famous needle in the haystack.

Many scientific studies have already attempted to answer these two questions using techniques that examine the expression of genes in thousands of individual cells at once.

- It turns out, however, that when you compare studies that actually try to answer the same questions, the answers are often not the same, says Jesper Grud Skat Madsen.

Are the patients or the researchers different?

This can be due to many different things:

- Maybe the people involved in the different studies are different and their disease or the mechanisms that have led to the disease are different. But it may also be that the people performing the experiments are different and that they perform or treat them a little differently. Regardless, it is very difficult to translate research that provides different answers into usable knowledge that can make a difference in the real world – because which answer is the right one?, Jesper Grud asks Skat Madsen and continues:

- When the answers are not the same between studies, you can popularly say that the haystack gets bigger and bigger, and it becomes harder and harder to find the needle.

- Therefore, it is important to understand the differences between studies. If the reason for the differences is that disease mechanisms are different, we should perhaps divide the haystack into different haystacks, which may each have their own needle. But if the reason for the differences is that the experiments are a little different, we should look for common features in the studies and thus reduce the haystack instead of making it bigger.

Which significance will an answer have?

Jesper Grud Skat Madsen's dream is that it will be possible to develop new and better diagnostic and treatment options for type 2 diabetics and their subgroups.

- If we are to succeed, we must learn to understand the differences between a large number of studies of type 2 diabetes, so that we can utilise that knowledge to prioritise between genes and factors, he says.

In addition to looking ahead, the research must also look back – and do so critically. We need to get better at comparing across studies and using all the knowledge we have in common, he believes.

- In my research group, we have just started a new large project, where we re-analyse large amounts of data with standardised and modern techniques to reduce differences that are not due to biological diversity - in the end, we hope that it can create new insight in type 2 diabetes. It requires people with different competencies in data science, statistics and molecular biology to work together across their fields, says Jesper Grud Skat Madsen.

What is it you don't understand

Researchers are constantly learning more about their field - but at the same time there is still a lot they do not yet understand. What is that? And what significance will it have for their research - and for society - to find answers? We ask SDU researchers.

Meet the researcher

Jesper Grud Skat Madsen is a molecular biologist and concerned with understanding the role of genes when we develop diabetes. He specializes in "computational biology"; moving traditional lab work into the computer and let the computer do the research and experiments. He is particularly interested in how metabolic tissues - the organs in the body that control our metabolism, such as the pancreas - change when we become ill with type 2 diabetes or obesity.

Editing was completed: 07.03.2022