Dysautonomia
Foundation Research --
Current Projects
Jesper Svejstrup
IKAP and its role as a component of the Elongator complex
Whereas
the clinical features of Familial Dysautonomia (FD) has been the subject of
several studies over the years, the molecular basis for it has remained elusive.
However, the recent mapping of FD-causing mutations to the gene named IKAP gives
new hope for understanding the biological pathways that are disturbed in FD
patient and thereby in the long term for devising a treatment.
Our work has so far been focused on how the information encoded by our genes is
read by cells, namely RNA polymerase II (RNAPII) transcription. The
enzymatic machinery allowing transcription is remarkably conserved from the
lowly single-celled yeasts to humans, and our first work on a factor that allows
efficient transcription was performed in yeast. This factor, called Elongator
(because it helps RNAPII elongate the RNA transcript that is made from
DNA), is also highly conserved, which allowed us to recently isolate its human
counterpart. One of the proteins in the human Elongator complex turned out to be
encoded by IKAP, raising the possibility that the function of Elongator is
disturbed in FD patients.
The work under the grant from the Dysautonomia Foundation will be focused on investigating whether this hypothesis holds true. We have several biochemical assays and cellular assays for Elongator function and will use these to compare 'FD Elongator' with 'normal' Elongator. We will also identify the other proteins in the Elongator complex (IKAP is just one of six proteins) and thereby their encoding genes. This might enable identification of the gene(s) responsible for non-IKAP associated FD.
We hope that our studies will help improve our basic knowledge of the molecular processes that are impaired in FD patients.
Jesper Svejstrup, Ph. D.
ICRF Clare Hall
Laboratories
Hertfordshire, UK
I received my Ph.D. degree from Aarhus University, Denmark, in 1993 and then did three years of postdoctoral research at the Department of Structural Biology at Stanford University. I joined the faculty at the Imperial Cancer Research Fund (now called Cancer Research UK) in 1996. My research has been focused on understanding the mechanism of transcriptional elongation. We employ a variety of biochemical, genetic, and molecular biology techniques to study the relationship between transcription, chromatin remodeling and DNA repair in model systems such as the yeast, Saccharomyces cerevisiae, as well as in human cells.