Published: 09-10-2015 17:26 | Updated: 26-10-2015 15:22

Karolinska Institutet researchers to receive SEK 150 million from the Knut and Alice Wallenberg Foundation

The Knut and Alice Wallenberg Foundation has decided to award close to SEK 133 million to fund research on embryonic stem cells, cancer treatments, brain research and possible causes of infertility, as well as SEK 16 million in continued funding for a research project on hereditary blood lipid disorders.

Investigating the mechanisms behind more effective cancer treatments

Professor Elias Arnér at the Department of Medical Biochemistry and Biophysics will receive SEK 43.7 million over five years for a project involving a total of seven research teams exploring how modulation of reactive oxygen species (ROS) could improve the treatment of various cancers. They will focus their initial research on melanomas and lung cancer.

“High levels of ROS may have a direct effect on destroying cancer cells; at the same time, ROS can also counteract the immune system’s ability to recognise and eliminate cancer cells. Our hypothesis is that it is possible to develop more effective cancer treatments by increasing ROS levels in cancer cells, while simultaneously reducing ROS levels in cells of the immune system,” says Elias Arnér.

Single-cell analysis gives an understanding of complex biological processes at the systemic level

Professor Sten Linnarsson at the Department of Medical Biochemistry and Biophysics will receive SEK 26.8 million over five years to investigate, through DNA sequencing, the mechanisms that allow cells in specific organs to specialise on certain functions. This fundamental research will be of great significance for our basic understanding of the body’s building blocks: the cells. It will also provide a more detailed explanation of what goes wrong when gene regulation causes illness, e.g., in the case of tumours.

“We believe that a fundamental mechanism in the formation of specific cell types is modular gene regulation. In this project, we want to systematically discover and map this type of gene modules in the brain,” says Sten Linnarsson. “We will also map molecular enhancers, i.e., DNA sequences that control gene activity. Many types of cancers are caused by mutations in these enhancers, and if we can better understand how they regulate gene activity, we could by extension find or choose better drugs.”

Molecular mechanisms behind infertility

Juha Kere, Professor and Chief Physician at the Department of Biosciences and Nutrition, will receive SEK 17 million over five years to clarify the molecular and cellular mechanisms that regulate early embryo development and fertility. In addition to its inherent scientific value, this research also has clinical implications. The causes of infertility remain largely unknown, and there is a need to improve our understanding of the biological mechanisms that are critical to early embryo development and pregnancy. During the first week of development after fertilisation, the embryo must complete four critical processes: the fertilisation itself; the activation of the embryo's own genes; the specification of the placental cell lineage, foetal membranes and embryonal tissues; and finally the attachment to the uterus. It is in these early embryos that embryonal stem cells can be isolated. The project led by Juha Kere will combine the expertise of three research groups to reach an overarching understanding of how these four processes are regulated on the molecular level. The research program is closely linked to clinical work, facilitating the translation of findings to clinical practice.

Juha Kere. Foto: Ulf Sirborn“Our current knowledge of early embryo development is primarily based on studies in mice,” says Juha Kere. “The development of the human embryo, on the other hand, is poorly understood on the molecular and cellular level. In fact, the few comparative studies that have been conducted point to fundamental differences in the mechanisms that regulate both the early embryo and the pluripotent stem cells. Due to the rapid development of both RNA sequencing methods and gene modification technologies we can now study how genes are regulated in individual cells and then study their functions.”

Precision medicine to optimise therapies for cancer patients

Professor Olli Kallioniemi of Karolinska Institutet and SciLifeLab will receive SEK 46 million to develop new strategies and clinical collaborations in translational and precision medicine, using existing SciLifeLab technological platforms and developing new ones for rapid research application. The initial goal is to find targeted cancer therapies for patients with leukaemia. The researchers intend to create a platform for systematic precision medicine for leukaemia that can later be used for other forms of tissue tumours as well.

Olli Kallioniemi. Foto: Veikko Somerpuro “We will look at how cells or tumours from leukaemia patients respond to 461 cancer drugs and simultaneously identify genetic and molecular factors that influence the effect of these drugs,” says Olli Kallioniemi. “We systematically monitor cell growth, cell death, changes and signalling after the drug treatments. As this is done on patients undergoing treatment, the systematic drug profile could enable better choices in terms of medication in the future. We will be studying the genesis and development of cancer clones, how these adapt physically to drugs, and how resistance occurs. We are starting with leukaemia, in particular acute myeloid leukaemia, but we will also look at whether our platform is suitable for tissue tumours, including ovarian and kidney tumours.”

Mapping the genes that control elevated levels of blood lipids

Bo Angelin, Professor of Clinical Metabolism at the Department of Medicine, Huddinge, will receive SEK 16.2 million in continued funding for a project that was funded by the Knut and Alice Wallenberg Foundation in 2013.

“Hereditary blood lipid disorders are a common reason why relatively young individuals suffer from cardiovascular disease," says Professor Bo Angelin. "The disease requires early discovery and treatment, and our research will improve diagnostic and therapeutic techniques for this important patient group. If we can identify new disease-related genetic mutations, we'll also be able to develop new drugs of benefit to larger patient groups with high cardiovascular risk."

The Knut and Alice Wallenberg Foundation