Introduction
Short introduction of the Genetics Department
The instructions for life are laid down in the genetic information contained within the DNA molecule that harbours all our genes and is located in the nucleus of every cell of our body. Importantly, these instructions should function properly during the entire life span of an organism and should be transmitted faithfully over subsequent generations. However, ubiquitous DNA-damaging agents such as UV light and X-rays and numerous natural and man-made chemicals continuously threaten DNA integrity. In addition, DNA suffers constantly from the damaging effects of reactive oxygen species generated by our own respiration and other cellular metabolites. Also intrinsic chemical instability of DNA, leading to spontaneous loss of vital genetic information adds to the gradual erosion of our genes.
Spectacular progress of research in recent years has revealed the dramatic impact of DNA damage on human health. Damage to DNA can cause permanent errors in our genes, which may trigger uncontrolled cell proliferation and eventually cancer or when occurring in the germ line lead to inherited defects. In addition, as revealed by research conducted in our laboratory damage to our genes appears a major cause for ageing and ageing-associated diseases such as neurodegeneration, osteoporosis, and organ failure.
To prevent these deleterious consequences the DNA carries also instructions for its own care-taking apparatus. An important component of this self-protecting mechanism is comprised of an intricate network of DNA damage repair systems, which attempt to repair DNA lesions before they give rise to cancer, inborn diseases or cause cell death or permanent growth arrest contributing to ageing. The main focus of the research programmes in the department of genetics is to understand the molecular mechanism of DNA repair systems, to elucidate their biological functioning and determine their clinical impact.To this aim, our institute has taken an multidisciplinary approach involving cloning of relevant genes involved in different DNA-repair pathways, isolating of the corresponding proteins, analysis of DNA and repair proteins at biochemical or single molecule level, in vitro as well as in vivo assays. This has resulted in delineation of the main reaction mechanisms of various DNA repair systems, involving Nucleotide excision repair, homologues recombination and endjoining. Recently, we identified a potent ‘survival’ response to accumulating DNA damage, which shifts the use of energy resources from growth to maintenance and defences and is able to promote healthy aging. Also we study the molecular mechanism of the biological clock and its medical impact for cancer and aging.
To this aim a coherent, multidisciplinary approach is taken, ranging from the molecular, genetic, cellular and intact organism level using the mouse as model upto patients with inherited defects in DNA repair, causing strong cancer predisposition and/or dramatic premature aging. The research involves a wide variety of approaches varying from sophisticated single molecule techniques to highly dynamic studies in living cells and organs utilizing refined laser and microscopic methods and from modern molecular, cellular and mouse genetics technology to all state of the art ‘-omics’ applications, including bioinformatics.
The Institute of Genetics is part of the Leiden/Rotterdam research school Medical Genetics Centre South West Netherlands, the Cancer Genomics Center and the top research school Center for Biomedical Genetics. Support is obtained from all major national and international research funding organizations.