Skip to content

"We want to improve the fundamental understanding of disease models"

Dortmund, 16th August 2024

Decoding the unique signature of lipids (fats) is Prof Dr-Ing. Sven Heiles's area of expertise. As Head of the Lipidomics junior research group at ISAS, he is doing all he can to perform in-depth analyses on these biomolecules in tissue or blood, for example. He uses a special mass spectrometry imaging procedure to do this work. Together with his team and researchers from the Justus Liebig University Giessen, Heiles has succeeded in decoding the lipid signature of single cells for the first time. In this interview, the analytical chemist explains the benefits of single-cell analysis and why the researchers chose microglial cells, of all things, as their model.

Prof. Dr. Sven Heiles.

Sven Heiles holds a professorship at the University of Duisburg-Essen and heads the Lipidomics junior research group at ISAS.

© ISAS

What information can be gleaned from the lipid signatures of single cells?

Heiles: The specific pattern created by the quantity, type and spatial distribution of lipids is what we call the lipid signature. It gives us valuable information about the lipid metabolism, which can vary between people who are healthy and those who are ill. Until now we have only been able to decode lipid signatures for larger areas, such as tissue or blood samples. But recently we managed to decode single cells for the first time too. Through the example of microglial cells, we were able to show in a cell culture that genetically identical cells sometimes respond to stimulation completely differently at the lipid level. We saw, for instance, that microglial cells which are no longer functioning correctly accumulate more so called lipid droplets than normal microglial cells. We were able to make these droplet-shaped fat deposits and their molecular composition visible using mass spectrometry imaging, AP MALDI-MSI.

Why did you study microglial cells, of all things?

Heiles: Although microglial cells are incredibly fascinating, for us it was less about the cells themselves and more about their heterogeneous properties. We already know that genetically identical microglial cells are often very different at the transcription and protein level – meaning they have different phenotypes, or observable characteristics. Based on previous research, we expected that these different subtypes would also exhibit differences in terms of lipid metabolism. But until now the technology to prove this just did not exist. We wanted to study the microglial cells to ascertain whether it is possible in principle to make these differences visible using AP MALDI-MSI. Of course, we were also interested in finding out whether our method is sensitive enough and able to image metabolic products that are sufficiently relevant. The hard work was all worthwhile. We delivered the proof of concept and were therefore able to prove that our approach is suitable for investigating subtype heterogeneity amongst cells in a cell culture.

What is the benefit of using AP MALDI-MSI over other imaging procedures?

Heiles: There are a few different procedures for imaging cells in detail. In fluorescence microscopy, for example, specific dyes and the corresponding microscopes are used to make selected structures visible. This is a targeted approach, which allows certain parts of a cell to be visualised selectively. But what happens if we don't even know what we want to see or if no suitable fluorescent dyes exist? That's where AP MALDI-MSI comes in. We don't need any dyes and in principle anything that we are able to ionise, we can make visible. Plus, unlike in fluorescence microscopy, we are not making the dye visible, but the biomolecules themselves.

You've shown that your method works. What's next?

Heiles: Information about the metabolism of single cells could be really exciting, as it could give us a greater understanding of highly heterogeneous conditions such as heart attacks or tumours. Not every cell inside a tumour is identical. Factors such as the local environment and, consequently, the supply of nutrients may vary. Now that we know our method works in principle, we are already working on studying cardiac and tumour cells too. In the long term, however, we want to move away from cell cultures and optimise our method such that we can perform single-cell analyses on complex samples like tissue sections. If we can better understand how nutrients are supplied to single cells under real conditions, that could help to elucidate disease mechanisms related to the metabolism of cells. Ultimately, our technology aims to improve our fundamental understanding of disease models and so to further the development of new treatments, for example, together with partners from clinical practice.

 

Article Recommendation

Müller, M.A., Zweig, N., Spengler, B., Weinert, M., Heiles, S.

(2023) Lipid Signatures and Inter-Cellular Heterogeneity of Naive and Lipopolysaccharide-Stimulated Human Microglia-like Cells. Analytical Chemistry, 95, 11672 – 11679. https://doi.org/10.1021/acs.analchem.3c01533.

(Interview conducted by Cheyenne Peters and Luisa Becher.)

Find more information on the scientists approach on ISAS Kompakt at “Fatty” signatures: How lipid patterns can be used as a diagnostic tool.

Share

Further articles

8th November 2024

Using the Russian Doll Principle to Analyse Biological Structures

In the “AI-assisted imaging of large tissues” project, several ISAS research groups are working on combining various microscopic and mass spectrometric methods. Much like looking at a Russian doll, the team looks deeper into the biological structures of a sample with each step.

Flora Weber at the lightsheet fluorescence microscope.
31st October 2024

AI in Healthcare: Why Is it Better to Think Small Instead of Big?

Sustainability is an important topic when it comes to artificial intelligence in health research. A group of international researchers, including from ISAS, has been working on this topic and published a Perspective in Nature Machine Intelligence. In the interview, Prof Dr Yiyu Shi talks about the resource problem and possible solutions.

Portrait von Prof. Dr. Yiyu Shi.
25th October 2024

Valuable Connections: Dr Saskia Venne

Dr Saskia Venne completed her doctorate at ISAS from 2012 to 2016. Today she is a team leader at Boehringer Ingelheim Pharma. In this interview, she is the first to provides an insight into the valuable connections in- and outside the institute that current and former ISAS researchers will be reporting on in ISAS Kompakt over the coming weeks.

Dr. Saskia Venne.
21st October 2024

Between Progress and Footprint: Artificial Intelligence in Healthcare

The potential applications of artificial intelligence in healthcare are constantly increasing. However, with ever better and faster models, the question of sustainability is also coming to the fore. A group of international researchers, including Dr Jianxu Chen from ISAS's AMBIOM group, has been looking into the increased consumption of resources and possible solutions to the impending sustainability problem.

Dr. Jianxu Chen (links) und Prof. Dr. Yiyu Shi im Foyer des ISAS.
15th October 2024

Science Meets Art: Immersion in the Secret World of the Immune System

Diving into the smallest structures of the heart via microscope images? This was possible at the first Dortmund Science Night. "The secret world of the immune system", the immersive 3D experience by storyLab kiU at Fachhochschule Dortmund University of Applied Sciences and Arts and ISAS, gave visitors the chance to experience immune cells up close after a heart attack.

Das Foto zeigt (v.l.n.r.) Dr. Malte Roeßing, Dr. Ali Ata Tuz, Lara Janz, Flora Weber, Sara Regein und Cheyenne Peters vor dem Stand des ISAS bei der Science Night 2024.
20th September 2024

"Book a Scientist": Register Now for a Virtual Chat with Researchers

The format "Book a Scientist" offers those interested in science the opportunity to book individual appointments with researchers within the Leibniz Association. Among them are two ISAS researchers. Their topics are "overzealous" immune cells after a heart attack and animal experiments and their alternatives.

Book a Scientist.
10th September 2024

Fascinating Insights: Virtual World in the Classroom

What actually is reality? How do we perceive our environment? And how can augmented reality support researchers in their work? Along with class 3a of the Don Bosco elementary school in Bochum, two ISAS researchers explored these questions.

Marie steht im Klassenzimmer und trägt eine VR-Brille. In den Händen hält sie jeweils einen Controller.
29th August 2024

Protein interaction paralyses a young patient

Two mutations in the genetic material of a boy lead to the rare neuromuscular disease NEDHFBA. Investigations of the young patient's samples by researchers at Essen University Hospital and ISAS shed light on the previously unrecognized mechanisms behind the symptoms: Proteins influence the development of the rare disease.

Bild von Dr. Andreas Hentschel, Mitarbeiter in der Arbeitsgruppe Translationale Analytik.
8th August 2024

"Fatty" signatures: How lipid patterns can be used as a diagnostic tool

Microglial cells, the immune cells of the central nervous system, are known for their different appearances. In order to demonstrate this heterogeneity for the first time at the lipid and thus metabolic level for individual cells, a team of researchers has set itself a special analysis goal: Decoding the unique and "fatty" signatures of individual cells.

Das Foto zeigt Jun.-Prof. Dr.-Ing. Sven Heiles und Doktorandin Chiahsin Chi am MALDI-Massenspektrometer.