The biologist and geneticist, Dr. Zoltán Ivics, has been made a group leader at the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch for a period of 5 years. He started work at this national research laboratory in the northeast of Berlin this summer. Dr. Ivics` field of expertise involves transposable DNA elements, transposons for short, that can be found in the genomes of most (if not all) living organisms, from bacteria to humans. However, they are very rare as far as human disease is concerned, because as Dr. Ivics explained: ”In vertebrates, most of these elements are dead remnants of once active transposons that, after successfully colonizing the genomes of many different species, became inactivated by mutations.”
Sleeping Beauty – New Vector System for Gene Therapy?
Based on ancient genomic elements from fish which are presumed to have been active approximately 20 million years ago, Dr. Ivics and his colleagues have created an artificial transposon they have named ”Sleeping Beauty”. By cutting out all mutations in the transposon they have ”awakened it with a kiss”. Sleeping Beauty is made up of two components: the transposable DNA (or transposon), into which a therapeutic or any other gene can be inserted, and a protein factor (the transposase) necessary to insert the transposable element into the host cell´s DNA. ”Sleeping Beauty could turn out to be a new and efficient tool for gene therapy”, Dr. Ivics says. ”It integrates well into human chromosomes, and it maintains the expression of the transferred gene”, he explained. However, during the process of insertion into a gene, Sleeping Beauty, as all transposons do, may destroy the function of that gene. This is a potential problem which has to be resolved, before it can become an ”ideal” vehicle for gene therapy.
Transposon insertion into endogenous genes might be disadvantageous for human gene therapy, but it is clearly of benefit where gene identification by insertional inactivation is concerned. Dr. Ivics hopes that Sleeping Beauty will help identify some of the genes that play a role in vertebrate embryonic development, as well as those involved in human disease, by isolating their counterparts from model organisms such as fish, frogs, and mice.
The development of a new vector system for gene therapy and gene tagging is only one of a number of areas Dr. Ivics wants to concentrate on while at the MDC. ”Transposons learned how to coexist peacefully for millions of years with their host cells. However, what their function (if any) was is still unclear. Also, our knowledge about the molecular interactions that took place between transposons and their host cells during that period of peaceful coexistence is rather limited”, Dr. Ivics says. So he now wants to find out what active transposons do in vertebrates, and how their activity is regulated. Also, Dr. Ivics wants to know more about the transposase, the enzymatic factor of the process of transposition. The transposase has multiple functions – it cuts the transposon of its home site, finds the target DNA for the transposon and then inserts it into the host genome. One of the first tasks is to solve the crystal structure of this enzyme.
Dr. Zoltán Ivics is a native of Budapest (Hungary) and started his biological studies there in 1988. He went to the University of Minnesota (USA) in 1991 and gained his doctorate at the University of Agricultural Sciences, Gödöllô, Hungary, in 1994. He worked in Minnesota as a post-doc until 1997. He then went to the Netherlands Cancer Institute in Amsterdam and stayed there for two years before coming to Berlin-Buch this summer.
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