GRANTS. The Knut and Alice Wallenberg Foundation is now investing SEK 36.7 million in research on neuroblastoma, a form of childhood cancer, that is headed by Professor Ruth Palmer at the University of Gothenburg. The large grant gives researchers access to new top-class analytical methods.
The project is a collaboration among three research teams at Sahlgrenska Academy, the University of Gothenburg, and an equal number of teams at Karolinska Institutet.
“These six research teams will explore the biological mechanisms underlying neuroblastoma development together. The grant means that we will be able to intensify our collaboration and that we can invest in state-of-the-art and highly accurate technologies,” says Ruth.
Neuroblastoma arises in the part of our nervous system known as the sympathetic nervous system. Because this nervous system is located throughout the body, patients can develop neuroblastoma in many places, although it is most common for the tumor to occur near or in the adrenal gland. The disease afflicts in the order of 15 to 20 children in Sweden each year. Most patients are diagnosed before the age of two, with some children born with the disease. The disease occurs in in a spectrum that spans milder forms, which can spontaneously regress, to highly aggressive forms.
From developmental biology to treatment
The advanced methods that will be used in the project include single cell sequencing and specialized mass spectrometry based protein analyses. These ultramodern methods will generate large amounts of research data, which provides great opportunities for understanding in detail what leads to neuroblastoma. By mapping how molecular activity increases and decreases at the cellular level in neuroblastoma and putting these patterns of change in a developmental biology context, the possibilities of developing new treatments will also improve.
“Neuroblastoma causes 15 percent of all cancer deaths among children. It is a disease that comes in many guises, and because it is so heterogeneous, it is difficult to define exactly what drives the development of the disease,” says Ruth Palmer, noting that one of the main goals of the research is to save or at least extend life.
“We have good experience with this kind of interdisciplinary collaboration among clinical and basic science researchers, and we know that such collaboration can lead to improved survival among patients.”
In recent years the possibilities of tailoring treatment to each child’s needs has improved, in part because of research by Ruth Palmer and her colleagues. The Gothenburg researchers are experts in the protein anaplastic lymphoma kinase (ALK). Its natural function is to control cellular signaling and development, and the protein has been identified as an important mechanism behind several types of cancer, including neuroblastoma. The Gothenburg researchers have previously made several important discoveries about how this protein is regulated and operates. As recently as August, they were able to publish new results demonstrating that neuroblastoma with an incorrectly regulated ALK protein could be counteracted with targeted medication that inhibits the activity of the protein.
Combining various mouse models
The six collaborating research teams have access to various model systems, from simple fruit flies to more advanced, transgenic mice. The work with animal models will been supplemented by experimental analyses of cancer cells and other samples from patients with neuroblastoma.
“Because neuroblastoma is such a complex disease, it will be technically challenging to combine the various mouse models of neuroblastoma, but this should throw light on how neuroblastoma arises during embryonic development. We have to use mouse models to investigate the development of neuroblastoma from the very first structures that develop to form the sympathetic nervous system,” says Ruth.
Her colleagues at Karolinska Institutet (KI) are experts on the tissue from which neuroblastoma originates. There is also expertise at KI in the key mechanisms involved in the development of neuroblastoma.
Ruth Palmer is a professor of molecular cell biology, particularly intracellular signaling, at Sahlgrenska Academy, the University of Gothenburg. She is originally from Scotland and received her doctorate at Cancer Research UK in London in 1996. She has previously worked at the Salk Institute, San Diego, California, and Umeå University.
TEXT: ELIN LINDSTRÖM CLAESSEN
PHOTO: JOHAN WINGBORG