ROBERT

Robert Rap (23) studies Bioinfomatics. His internship lasted twenty weeks and took place at the Radboud University in Nijmegen. His research was part of a larger project that investigated the p53 gene. This gene is particularly important for research on a variety of cancers and affiliated drugs.

Understanding the working of p53

‘At the NCMLS (Nijmegen Centre of Molecular Life Sciences, part of the Radboud University) p53 is an important research topic. P53 is a protein which plays a major role in apoptosis, or regulated cell death. In about 60% of the cases, the occurrence of cancer can be traced back to a mutation in the gene that is coding for p53. Therefore, understanding the working of p53 is vital for developing new or better drugs and methods for diagnosis.’

Hundreds of genes regulated by a single protein

‘P53 binds to the DNA at a number of different locations. Directed by Professor Henk Stunnenberg, we performed a genome wide analysis to search for optional binding spots. We found out that p53 can bind the DNA on an astonishing amount of 1500 different spots! An important technique that was used for this analysis is working with microarays. A microarray is a tiny chip loaded with DNA that enables the researcher to analyse which genes in a sample are turned on or off. A single microarray assay already generates a large amount of data. This is where the bioinformatics comes in. A plausible hypothesis can be that p53 influences gene expression of genes nearby a binding spot. However, the idea that a single protein is a single chain in a cellular process is already proven to be a simplification. At present, proteins are placed in complex networks to describe cellular processes. Therefore, p63 and p73, proteins similar to p53, were also taken into account. These genes are also involved in apoptosis and they also affect hundreds of genes.’

The bioinformatician

‘Analysing datasets with thousands of gene locations by hand would take an enormous amount of time. The computer can be a valuable aid. Huge databases are freely available online. By comparing the information stored in these databases to the output of the microarray assay you can learn more about the working of p53, p63, p73, and the differences between these highly similar proteins. Since there is no straightforward method or software for this comparisson, the bioinformatician has to be creative in developing his own methods. Using his knowledge of biology, a bioinformatician aims to convert data into biological information. Bioinformaticians as you can see can be a valuable support for biologists in the laboratory.’

The internship

‘I used the first ten weeks of my internship to develop a method that links a function and description of a gene to a gene number. By comparing the gene descriptions and the cellualar processes they are involved in, I was able to compare the effect of p53, p63 and p73. These kind of methods can be made fully automated. The final ten weeks of my internship were dedicated to the biological interpretation of the results. During my internship there was a constant interaction between the scientists working in the laboratory and the ones working behind a computer. Because of my education in , I was able to understand both groups. I expect to graduate this year, and after that I hope to be able to continue working on this kind of projects.’