Studying the molecular puzzle of metabolism
When we eat, we consume protein, fats and carbohydrates, which are broken down in our stomachs and turned into sugar, amino acids and fatty acids. These are absorbed by our blood and transported to the cells in our bodies. Some of these substances are used to produce energy; others are made into building blocks to create proteins and hormones, etc. Everything is controlled by our metabolism.
“The metabolic system is like a big puzzle – all substances are connected to each other, and the more pieces you can add to the puzzle, that is, the more substances you study, the more you can learn about our metabolism”, says Peter Spégel.
There are many techniques to study the substances of our metabolism, the so-called metabolome, and mass spectrometry is one of them.
“It’s a way to measure molecules, such as glucose, fatty acids and amino acids. You start by charging the molecules that you want to measure. Then you can make them move freely within an electric field. By controlling the fields, these molecules can be sorted, counted and dissected. Metabolomics is about measuring as many small molecules as possible in blood or tissue”, he says.
Searching for patterns
Humans have different genetic variations; similarly, we have variations to our metabolism. Peter Spégel studies how these variations take place in different people, and how they relate to diabetes.
“I’m looking for metabolic patterns to try to describe how the different substances relate to one another, and how they change in cases of diabetes”, he says.
Metabolism is a process in itself, involving several steps, and Peter Spégel aims to find out exactly what goes wrong in cases of diabetes, saying that “the process can go wrong in several places”.
Today, such a study usually involves a couple of hundred so-called metabolites – substances or residual products from the decomposition of nutrients. Peter Spégel wants to significantly increase this number.
“In every analysis we see hundreds of metabolites that we are currently unable to identify. Once we know what they are, we will probably be able to understand significantly more about our metabolism. The metabolites that can be measured differ from one cell type to another”, he says.
Obtained a PhD in analytical chemical engineering
Peter Spégel received his doctoral degree in analytical chemical engineering at the Lund University Faculty of Engineering in 2007. Already at age 12, he knew he wanted to become an engineer, without having the faintest idea of what an engineer actually does.
“A friend of mine learned that less than one per cent of people in Sweden become engineers. He and I both saw this as a challenge. He is now a senior lecturer in food technology”, Peter Spégel says.
Because the upper-secondary school in Helsingborg which he attended shared its lab facilities with the Faculty of Engineering, there was opportunity to perform different types of experiments, which reinforced the career plans of this future engineer. It came natural to him to later apply to the MSc programme in Chemical Engineering.
“After completing my Master’s studies I felt that I wasn’t quite done – I wanted to learn more, and decided to apply for a doctoral studentship”, he says.
This became a rough period of his life. The department’s finances were shaky, and times were tough with cutbacks and conflicts.
“When I received my PhD I thought to myself ‘no more academia’ – that was the image I had at the time”, he says.
However, another one of his friends, whose girlfriend was situated at the Lund University Diabetes Centre, LUDC, had heard that the centre was looking to appoint someone who could establish a platform for metabolomics, and convinced him to apply for the position.
“My image of academia back then was not accurate; I had simply been in the wrong place at the wrong time. Then I discovered that academia can be both really fun and exciting”, he says.
Immersed in medical issues
The beginning of his time as postdoc in Hindrik Mulder’s research group, he spent setting up the new technique, mass spectrometry, and felt right at home. The medical applications and his knowledge of metabolism and beta cells came later.
“When I had been in the lab for one month, all of my fellow lab colleagues were heading to the annual conference of the European Association for the Study of Diabetes, EASD. I was then placed in charge of looking after everyone’s cell cultivations, 50–60 of them, so you can say that I gained all my practical knowledge within the scope of that one week”, he says.
Over time, he became immersed in issues in the field of medicine.
“I find it tremendously exciting! Unlike engineering subjects where there is usually only one answer to a question, there is much more discussion within medical research”, he says.
Exclusive access to beta cells
As a researcher at the Lund University Diabetes Centre, Peter Spégel has access to pancreatic islets from deceased donors. Because of their placement inside the pancreas – a sensitive organ permeated with a lot of blood vessels – the islets are inaccessible in humans and animals who are alive.
“Having access to donated cells is very exclusive. However, although it is a huge advantage to have access to human islets, one must not forget about animal and cell models. There is a huge variation in the islets and we still have a lot of basic research to do, so understanding basic functions, animal models and cultivated cells is also important”, says Peter Spégel, and continues:
“When it comes to more basic metabolic functions, humans and animals are not always very different. Pancreatic islets in all species secrete insulin when exposed to sugar.”
Changes in metabolism in cases of diabetes
The questions he wants answered are: What changes in the metabolism are connected to the development of diabetes; what changes occur before developing diabetes and which are linked to getting rid of one’s diabetes through e.g. obesity surgery?
“The hope is that we will find not only one metabolite but several that together form a pattern, otherwise the instrument we use to understand the disease will become as blunt as it is today when only measuring one metabolite, glucose”, says Peter Spégel.
The biggest challenge is time
The biggest challenge in his work is time.
“Metabolism/metabolome contains a lot of information. However, it is also affected by a large number of factors: what we eat, what genes we have, if we are stressed or ill. The difference between being healthy or ill can involve a twenty per cent increase of a certain metabolite; meanwhile, the same metabolite can be affected almost just as much after we have just eaten or from stress. Therefore, we must analyse a large quantity of samples, which is still very time-consuming”, he says, and continues:
“There is no ‘plug and play’ function – contrary to popular belief, you don’t just insert a sample and out comes the result. The road that leads to the data in your Excel sheet can be quite a struggle.”
Peter Spégel’s research has resulted in the discovery of an active metabolic pathway inside the beta cell, which was previously believed to be inactive.
“We saw that products were formed, which simply indicated that it was active. When we shut it down, the insulin release drastically reduced, which would not have been the case if it were inactive. Since then, our work has been followed by several studies by other research groups, who are exploring this part of metabolism even further, so it feels like an important discovery”, he says.
A new classification sytem for diabetes
The goal of his research is to create a new classification system for diabetes, based on metabolism.
“Today it is based on the clinical image. I believe that by knowing exactly in what way your metabolism is disturbed, it will also be possible to tell whether or not you will respond better or worse to medication”, he says.
He also wants to study which types of metabolism there are in different groups of people.
“Your metabolism might be different from others without being diseased. There is a lot of variation between us – can this variation be described somehow? If you have a certain type of metabolism, you might have a certain risk of developing the disease”, he says.
Active in his spear time
Although at work he is always under heavy time constraints, outside of work Peter Spégel is less pressed for time. Up until last year he was a beekeeper, but he grew sensitive to the bee stings so he instead embarked on a new project: to build a road of 150 metres that lead to his family’s holiday home. He will be digging, laying gravel, and cutting down trees – by hand.
“I figure it will take 15 years to complete, but I’m not stressed. I find it relaxing, as in my job I never see any physical results, only an abstract image of reality”, he says, and continues:
“I do a lot of sitting down while at work, so in my spare time, I have no need to sit still and watch TV or read a book.”
His accomplishments also include winning a silver medal in the Swedish Youth Championships in relay swimming, as well as a black belt in judo. As a result of various injuries, however, he has now discontinued all sports activities.
Bridge between engineering and medicine
In the future, Peter Spégel hopes to become a bridge between research in medicine and engineering by working in a more interdisciplinary manner.
“I see it as an advantage to have a foot in each field. Diabetes research needs technology and technology needs applications”, he says and continues:
“Metabolomics is a discipline that is both heavy in technology and application-driven, and by strengthening the connection between the research fields of engineering and medicine, we can secure technical infrastructure and expertise for diabetes research.”
Text: Sara Liedholm
Pictures: Sara Liedholm (portrait), others private