Today, anyone can have their DNA mapped for 1,000 euros. We all inherit a complete set of genes from our father and mother, but it is more interesting to know how and why a gene from one parent has a stronger effect on the child than a gene from the other parent. In other words: which mutations lead to which gene expressions in a child? And what is the role of the parts of our DNA that do not contain genes? The young bioinformatics researcher Elzo de Wit was awarded an ERC Starting Grant to study this. "Gene technology is a rapidly evolving field, and the advances are having a major impact. Just imagine being able to identify a child’s health risks in life in advance!"
My own lab
In his work, De Wit links bioinformatics (the calculation and analysis of big data) to biotechnology, achieving a unique 'wet and dry lab' combination. "I've been playing around with computers since I was a young boy in the 1980s. I went on to study Biology, and during that time I also became fascinated by cell processes. I was inspired by the fact that we are able to study human cells at molecular level. I did my PhD research at a time when big data was an emerging concept, and I was able to combine both skills." In September 2015, the young researcher will move from the Science Park in Utrecht to Amsterdam. "Thanks to the ERC grant, I will be able to concentrate on my own research for the next five years. The Netherlands Cancer Institute is allowing me to set up my own lab there.
Gene mutations, breast cancer and folding ability of DNA
In his lab, De Wit will first analyse the gene mutations in the human genome and study their effects on gene expression, the visible differences between individuals. For example: which parent’s genes determine a child’s height, and to what extent? Which genes are responsible for the risk of high blood pressure? "The human genome comprises 3 billion base pairs, and an individual genome contains approximately 3 million inherited variants (mutations). However, not every mutation has an effect. So the question is, which ones do? To what extent, and on what?" De Wit is particularly interested in how genes are regulated by the area around them. For this large-scale DNA analysis he uses various data sets of human cell lines. "I am working with genetically stable cell lines derived from white blood cells. The great thing about ‘computational biology’ is that the computers can detect patterns that would otherwise remain undiscovered because the data are so complex.”
De Wit’s work will also focus on breast cancer. It is known that mutations in the BRCA1 and the BRCA2 gene can lead to a congenitally increased risk of breast cancer. But in some cases an increased risk of[ER1] familial breast cancer exists without there being a mutation in these genes. “This may be due not to the gene itself, but to the effects of the non-protein-coding area around it. In Utrecht we developed a technique for analysing the DNA that surrounds genes. This technique enables us to map the full spectrum of genetic variation. This is likely to lead to a new dimension in research. For this research, I will select families and set up control groups in Amsterdam."
A third aspect of the research is the complex folding ability of our DNA. "A cell contains about 2 metres of DNA, but in some cases the diameter of the nucleus in which it has to fit is no more than 5 micrometres. The question is, how is it possible for DNA to be folded so efficiently, in a way that maintains accessibility to all its elements? We already know that long-distance activation of genes is possible in the DNA, through elements moving towards the gene. I will develop a method for studying that process."
DNA research is booming. It is not inconceivable that, in the future, we will be able to predict which mutations can lead to which gene expression. Personalised medicine is the next step forward. De Wit: "DNA is what makes us human. It is one of the things that defines our identity. In my view, the advances in this field are comparable to the rise of the personal computer in the 1980s. It is set to impact our lives in unimaginably profound ways."
Text: Youetta Visser