She reveals the molecular advances in cells
4 april 2017
What happens in cells when the molecular composition changes? In her research, analytical chemist Ingela Lanekoff at the Department of Chemistry-BMC, tracks the progress of small molecules or metabolites. “We are focusing on seeing things that nobody else can see in cell tissues. By measuring and determining the significance of molecular processes, we can better understand disease progression.”
With the molecules of the human body in balance, our bodies work as they should. But any disturbances will increase the risk of illness and disease. What causes such processes and for example leads to tissue dying remains unknown to scientists. But one important step is to capture images of molecules in tissues and thereby track changes. One way to do this is to use nano-DESI MSI, which is short for nanospray desorption electrospray ionization mass spectrometry imaging. Currently, in Sweden, it is one of only two ways to analyse molecules on sample surfaces without first placing the samples in a vacuum, says Ingela Lanekoff.
“One benefit of nano-DESI technology is that we can determine the amount of each molecule present on the tissue surface. Also, we can analyse the samples directly in atmospheric pressure without any special sample treatment. We register the molecules’ positions in the tissue samples using an analytical instrument called a mass spectrometer; then we put together images that show where individual molecules are located.”
Ingela Lanekoff brings out two capillaries, thin glass tubes with inner diameters of 150 micrometres, roughly equivalent to two hairs. A mix of methanol and water is led into one end of the first capillary, forming a drop at the other end which acts as a liquid bridge to the second capillary.
“When the drop touches a surface, molecules from that surface will dissolve and transfer to the drop,” says Ingela Lanekoff. “The molecules are then transported by the solvent through the tube to the mass spectrometer where they are recorded.”
Tracks chemical processes
The suction effect is caused by the closeness to the mass spectrometer’s vacuum. Ingela Lanekoff’s research group has recently developed a method that uses gas to move the solvent through the second glass tube.
“Using a gas flow, we can combine different solvents that get through the capillaries more easily. It makes the process more stable. We have already been able to detect a stronger signal of small molecules called metabolites.”
Metabolites brings to mind metabolism and the body’s digestion of food, but according to Ingela Lanekoff, the mission of these molecules includes other things too.
“Each individual cell has its own metabolism. If you have abnormalities in one cell, the cell will send out chemical signals in the form of metabolites, which affects surrounding cells. This may be the result of a medical condition. For example, if a cell begins to reproduce more and changes its metabolism, it may be cancer. By tracking the metabolic pathways within cells, we get a picture of which chemical reactions and processes have taken place.”
The technology is used for all types of tissues but Ingela Lanekoff’s group focuses mostly on imaging the kidney and brain. The surface to be analysed can be as small as one tenth of a millimetre in diameter, making it a great challenge to record molecules in the mass spectrometer.
Developed new measuring technique
But already as a post doc, Ingela Lanekoff developed a method for correctly measuring and recording concentrations of molecules that are converted into ions. The method uses molecules from a similar substance, a so called standard, which are introduced into the solvent in the glass capillaries. At ionization, the molecules of both substances behave in the same way. What sets them apart are their differences in weight. In this way, the researchers can determine the concentration of a certain substance in a sample.
“This quantitative method is probably what I’m most proud of. It has become an accepted method for imaging of molecules and is used, among others, by a lab for characterisation of microbial samples,” says Ingela Lanekoff.
She is approached by many who want to work with her group, both from within Uppsala University, at Karolinska Institutet and companies like Astra Zeneca – and by many abroad.
“But you can’t do everything, you have to focus on a few projects. We would first like to see how far we can take this method. How much can we see, how sensitive and specific can we be? What is it we can do that no one else can do?”
In 2015, she and 11 young scientists received the Ingvar Carlsson Award from the Swedish Foundation for Strategic Research. The allocation of SEK 4 million allowed her to hire a post doc, with another joining soon. She also supervises two doctoral students, one as main supervisor and the other as a co-supervisor in collaboration with organic chemistry. In addition, she accepts students doing degree projects, upper secondary students and university students for summer projects. On top of that, she teaches analytical chemistry at Bachelor’s and Master’s level.
“You learn a lot by teaching, and I enjoy it. Sure, it takes time, but in order to secure tomorrow’s chemists, it is very important for us at the university to motivate young people and get them interested in chemistry.”
FACTS INGELA LANEKOFF
Title: Postdoctoral research fellow in Analytical Chemistry, Department of Chemistry, Uppsala Biomedical Centre
Family: Husband, a daughter and son in their teens
Interests: Reading, walking or cooking, usually quieter activities to get some recuperation. Music used to be an important part of my life; I sing and play, mostly cello but also piano and guitar. But now I’m in a different phase.
Strength: It’s probably both a strength and a weakness that I am constantly reflecting on and analysing situations and interactions with people, both in and outside the lab. I’m very fascinated by people and human behaviour. When you are in a team leadership role, it is important to try to understand why people behave the way they do.
If I had not become a scientist: After upper secondary school, I wanted to work with people and become a human resources specialist. But then I thought chemistry was fun, so I decided to go for that instead. And somehow, I now combine both interests. I enjoy working with people, watching them develop, supporting them as much as I can. At the same time, doing research is very exciting, especially when you have an idea about something working a certain way and you continue to try and try again and then all of a sudden like “wow, it worked!”
The surname Lanekoff: My name used to be Andersson and my husband’s Johansson and even before we were engaged, he thought Johansson was a really boring name. So he decided to change his last name to Lanekoff from the Swedish rhyme Ole dole doff, kinke lane koff... When we got married, I took that name as well. But when our daughter was born and my husband thought it would be fun if she was named ‘Kinke’, I said that’s where my humour ends, hah!