Important brain discoveries

The Norwegian Centre for Molecular Biology and Neuroscience (CMBN) at the University of Oslo (UiO) was among the initial 13 Norwegian Centres of Excellence (SFF) established. After ten years, its activities as an SFF centre are drawing to a close.

Photo: Pål Mugaas INTERNATIONAL GROUP: Tone Tønjum together with researcher Seetha Balasingham and technical assistant Marta Gomez Muñoz (front) at one of the CMBN offices. (Photo: Pål Mugaas)

 

An ambitious objective

Back in 2002, the aim was to bring together expertise from the fields of molecular biology and neuroscience and specialise in research on the ability of genes (DNA) to repair themselves and of neurons to communicate with one another.

DNA is continuously exposed to environmental factors and metabolic changes within the cell that can lead to damage. If the damage is not repaired it may lead to illness and/or lasting changes in the genetic code. Since most brain cells do not divide, their capacity for DNA repair is particularly essential.

“The centre’s vision has been very important to us. With approximately 200 people working in 11 different groups at the centre it is vital to have a mission to share in order to achieve a unified approach,” explains Professor Tone Tønjum. She took over as centre director in 2009 for Ole Petter Ottersen, who was elected Rector at UiO.

The current director stresses the significance of the work carried out during the early years of the centre under Dr Ottersen and Dr Erling Seeberg, who died in 2004. Assistant Director, Jon Storm-Mathisen, has also been a linchpin of the centre’s activities, Dr Tønjum states.

Illustration: CMBN Researchers at CMBN have demonstrated that DNA repair in the brain is highly effective. (Illustration: CMBN) Great potential for treating Huntington’s and Alzheimer’s disease

Each day the genetic material within every single neuron in the human body is damaged between 20,000 and 70,000 times. When the centre launched its activities in 2002 researchers had no real idea of the extent of DNA repair taking place in neurons and the surrounding glial cells in the brain.

“Our researchers have demonstrated that DNA repair in the brain is highly effective. In doing so, we have made valuable discoveries about brain structure, function and plasticity (development potential) – mechanisms that provide an explanation for memory, learning and adaptation. The significance of defects in the DNA repair system has also been documented and we now embark upon a new decade of revised and expanded challenges,” Dr Tønjum claims.

New areas of research she points to include studies of individual glial cells and of DNA repair in connection with inflammation and bioenergetics (energy transfer and conversion within mitochondria).

The centre’s research is of major importance for understanding illnesses such as Huntington’s disease and Alzheimer’s disease. The goal is to build a knowledge base of new methods for diagnosing and treating brain disease and age-related neurological disorders.

Water transport and inflammation

Aquaporins are proteins regulating the transport of water through a cell’s membrane. In 2006, researchers under Dr Ole Petter Ottersen at the CMBN discovered that aquaporin 4 (AQP4) was the dominant water channel in the brain and thus a key factor in the development of brain oedema. Oedema is an accumulation of fluid outside blood vessels, which can have fatal consequences when it occurs in the brain.

“Aquaporins proved to be associated with a large number of disorders – everything from strokes, brain oedema and meningitis to inflammatory bowel disease,” Dr Tønjum explains. She points out that the research at the CMBN is carried out in close cooperation with Oslo University Hospital (OUS). This collaboration creates immediate benefits for translational research (medical research that bridges the gap from basic research to clinical research, editor’s note).

Several interdisciplinary research projects have been initiated in the wake of these discoveries. Using the centre’s powerful in vivo photographic equipment, researchers plan to determine the feasibility of targeting these water channels in the treatment of strokes and meningitis. The equipment makes it possible to photograph living organisms so that it is possible to see the physical and chemical processes within a cell as they take place.

Photo: Pål Mugaas The investment in technology has enabled us to develop a vast amount of expertise, says Professor Tone Tønjum. (Photo: Pål Mugaas) Continuing support for infrastructure and knowledge-building

Over 600 publications and 49 Ph.D. degrees are important achievements, but Dr Tønjum is more concerned with the quality, not the quantity, of the centre’s research.

“Over the years, we have witnessed the emergence of a young, highly skilled interdisciplinary environment with people who are good at asking each other pertinent questions. The investment in technology has enabled us to develop a vast amount of expertise that we are now trying to continue by means of a good exit strategy,” Dr Tønjum states.

The centre has decided to invest heavily in technological infrastructure. As much as 35 per cent of the allocations from the Research Council of Norway have been set aside for strategic collaborative investments leading to the acquisition of a substantial amount of advanced equipment. In November 2011 the CMBN, together with the Centre for the Biology of Memory and the Medical Imaging Laboratory (MI LAB) – both at the Norwegian University of Science and Technology, was awarded NOK 80 million to establish a new national research infrastructure project, the Norwegian Brain Initiative – A Large-scale Infrastructure for 21st Century Neuroscience (NORBRAIN).

“The Research Council has really put muscle into this initiative. And, the University of Oslo and the Oslo University Hospital have done a terrific job as the host for a colossus like our centre,” Dr Tønjum points out.

In May 2012 Dr Tønjum submitted a report to its host institutions on the activities and plans of the CMBN. The report summarised the centre’s most important findings and breakthroughs over the past ten years and outlined how the established knowledge community and the technical infrastructure in NORBRAIN, among other activities, should be continued. “A project such as this is only as successful as its exit strategy. We believe that we have prepared for this through the report and the plans we have made for the future.” Professor Tønjum concludes.

Centre for Molecular Biology and Neuroscience (CMBN)
  • Objective: To understand how neurons communicate with each other, determine their role in DNA repair and damage and understand other genome maintenance mechanisms that play a role in brain health, aging and illness.
  • Participants: The centre is comprised of 11 research groups.
  • Annual allocation from the Research Council of Norway: NOK 20.7 million.
  • Total annual budget: NOK 130.2 million from UiO, OUS and other sources. Over the entire ten-year period: between NOK 80 million and NOK 130 million (i.e. self-financed: 25 per cent, Research Council: 15-20 per cent and others: 50-55 per cent).
  • Total man-years: Approximately 200 researchers and students.

www.cmbn.no

 

 

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