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Hunter of galectines

Conductors of the immune system

Ulf Nilsson.

Ulf Nilsson is professor of Organic Chemistry and dedicates most of his research to drugs, creating new molecules which bind proteins. In recent years, a type of proteins known as galectins has proven to be of great interest. They are part of the immune system of humans and animals and have shown to play a major role in both inflammation and cancer.

Around these substances, a large and active group of researchers has grown in an extremely interdisciplinary network, which is, however, completely informal and includes researchers from the faculties of medicine, engineering and science.

“It was Hakon Leffler at the Faculty of Medicine who returned 14 years ago to Lund from UCS in California, where he had discovered these substances. I had just returned from a post-doc in Canada and we started to work together. Since then, research has been ongoing first with one doctoral student and then growing organically, generating good results, good colleagues and increasing grants”, says Ulf Nilsson. The studies have gone from basic research and theory to experiments on both animals and humans. Theory, calculation methods, quantum physics and experiments on animals and soon people.

Five or six research teams are currently working in Lund with around 20 international more or less active collaborations. A year ago, Ulf was working with the company Galecto Biotech AB on fibrosis in the lung. “Fibrosis is scarring which can be very extensive and problematic. There are no drugs at all for the condition and our drug works (reducing the fibrosis) in animal experiments. It will soon be tested on humans. Now we are dealing more with product development than research” says Nilsson. The company is Swedish and has been successful in attracting venture capital, but it is located in Copenhagen in the Cobis business incubator with Danish staff and funding which is three-quarters Danish”.

The researchers are pursuing work on both the biology and the chemistry behind galectins. Derek Logan, senior lecturer in molecular biophysics, uses x-rays and neutrons to study their structure and is therefore waiting eagerly for ESS. Mikael Akke at LTH is investigating their flexibility, how they change and move. The dynamic determines in many cases how well they bind, providing a fantastic tool once the process is understood.

Ulf Nilsson is mainly investigating the chemistry and how one can make new synthetic molecules which bind to the galectins. Ulf’s team comprises eight researchers and a number of degree project students who according to him “make fantastic contributions”.

“Nowadays we can produce almost all the galectin-inhibiting molecules we want” he says. “And yet we can’t calculate by computer exactly how a molecule should be constructed; there is a lot of trial and error before we get it right”.

“The inflammation situation is very reminiscent of cancer in certain cases. Sometimes the immune reaction can even benefit the cancer. In that case, the ability to affect the immune response can be valuable. Together with researchers at the Biology building and BMC as well as in Brussels and London, we have got exciting results on this. The results – both on cells and on mice – are positive but remain on the level of basic research. The main reason is the enormous competition that prevails between thousands of biotech companies in the field of cancer. The marketing costs can then easily become insurmountable, as I have found out.”

“But if something really exciting comes up we can make an attempt, for instance linked to diagnosis where we can contribute to the treatment of some specific tumour.”

Ulf is also running a project with exciting discoveries on malaria and enzymes. And yet here too, it is hard to achieve commercial viability. Other research is aimed at NRC, the Neuronano Research Centre, and the chemistry around electrodes in the brain.

When Ulf isn’t working, he spends his time on his children, sports, outdoor activities and his house in Håstad. Just as other professors, he works in the lab extremely rarely, which he had trouble getting used to at first.

Text and images: MATS NYGREN

 

Facts / Galectins

A galectine protein with an articial molecule that bind with it.

Galectins are proteins on the surface of cells where they bind to complex carbohydrates. They signal to other proteins when the cell is attacked and function in this way as conductors in the immune response. The researchers have found 14 different varieties with different functions. Thus they operate at a higher level than inhibitors and substances currently used in cancer therapy. Some affect the T-cells and macrophages, which are important in healing and fibrosis. Too many macrophages lead to excessive scarring, a problem in heart attacks and lung fibrosis.
The research is conducted using many advanced methods such as x-ray and neutron crystallography, nuclear magnetic resonance, biochemical analysis, thermo-chemistry, computational chemistry and mathematical analysis – to name but a few.