Heutink: hunting genes that bring diseases to the mind
If a neurological disease is hiding in the genes, then Peter Heutink is determined to find it. Using both genome-wide screening methods and targeted genetic tests, the professor in Medical Genomics works on the genetic background of neurological disease, and especially neurodegenerative disorders like Alzheimer's and Parkinson's.
To identify genes associated with disease, Heutink and his group use two different strategies. On one hand, they collaborate with neurologists in the clinic to trace families in which a disease segregatesand try to identify the genes that are involved. The other approach is to screen groups of unrelated patients, aiming to find shared genetic variance that could predispose carriers to illness of the brain.
Using families with a known predisposition to a specific neurological disorder, Heutink tries to find the genetic substrate of that vulnerability. Heutink: 'We keep close contact with the clinical departments, because of our need of well-characterized patients. One of our activities is studying families that carry a higher risk for a certain disease. This link with clinical practice certainly has advantages for the patients: if we for example find a genetic cause for a condition, we can directly use this knowledge for diagnostic purposes. And once we find such a genetic predisposition, we also start investigations into the mechanisms that eventually lead to the illness. For that type of fundamental research it is really great to have specialists in for example biochemistry and neurobiology around. The Neuroscience Campus is only going to improve those opportunities of collaboration.'
As a parallel approach, Heutink screens the genetic make-up of large groups of patients, and compares them to equally large groups of normal, non-diseased controls. Heutink explains: 'Basically, we search for stretches of DNA that are more common in patients than in healthy people. If we find such a shared genomic region, we focus on the genes that are coded in that part of the DNA to select possible candidates that could cause neurological disease. Once we have the candidate genes, we examine the sequences to find mutations that could cause explain the fenotype.
Subtle phenotypes
'Eventually we want to find ways to define ways to undo the disease-causing mechanisms, for example by addition of chemicals with a therapeutical intention. For that purpose we now started a collaboration with Prof. Guus Smit of the department of Molecular and Cellular Neurobiology, using high-throughput cellular assays that can screen thousands of genes and/or compounds for their potency to change neuronal phenotypes. The strengths of this system are that cell culture can be completely automated for high throughput but the microscopical analysis is still very detailed and can measure subtle phenotypes such as neuronal outgrowth or subcellular locations of certain proteins. We have high expectations of that collaboration.'
Heutink's research is already strongly interconnected with other departments on the VU campus, but the Neuroscience Campus Amsterdam will provide even more possibilities for co-operation, Heutink predicts. 'For us as genetic scientists the situation is perfect: we are close to the clinical practice, but also share offices and facilities with fundamental researchers. It is my strong belief that if you bring scientists together physically, there will grow mutual understanding for the respective fields of interest. Understanding leads to collaboration, and promising projects will be mushrooming.'
