Arthur Günzl, Ph.D.Professor, Genetics and Genome Sciences
|M.S.||University of Tübingen and Duke University||Biological Sciences|
|Ph.D.||University of Tübingen||MPI Biological Sciences|
|Fellowship||German Academic Exchange Service (DAAD)||Graduate Student Fellowship|
|Postdoctoral||Max-Planck-Institute for Molecular Genetics||Post-doctoral Fellow under Dr Albrecht Bindereif|
|Postdoctoral||Yale University School of Medicine||Post-doctoral Fellow under Dr. Elisabetta Ullu and Dr. Christian Tschudi|
|Fellowship||Excellence in the Life Sciences (EMBO), Germany||EMBO long term fellowship|
|Name & Description||Category||Role||Type||Scope||Start Year||End Year|
|The NIH IDMR02 Special Emphasis Review Panel||Study Section||Ad hoc reviewer||External||National||2012||2012|
|the NIH IDM-M (Eukaryotic Pathogens and Vectors)||Study Section||Ad hoc reviewer||External||National||2012||2012|
|the NIH TMRC (tropical medicine research centers) study section||Study Section||Ad hoc reviewer||External||National||2011||2011|
|the NIH ZRG1 IDM-R Special Emphasis Review Panel||Study Section||Ad hoc reviewer||External||National||2010||2010|
|the NIH ZRG1 IDM-B Special Emphasis Review Panel||Study Section||Ad hoc reviewer||External||National||2010||2010|
|Eukaryotic Cell||Editorial Board||Member||External||National||2010||2012|
|New England Association of Parasitologists||Professional/Scientific Organization||Member||External||Regional||2009|
|Molecular and Biochemical Parasitology||Study Section||Ad hoc reviewer||External||International||2008||2012|
|the Wellcome Trust, UK||Study Section||Ad hoc reviewer||External||International||2008||2012|
|the Ohio Cancer Society||Study Section||Ad hoc reviewer||External||National||2008||2012|
|the US-Israel Binational Science Foundation||Study Section||Ad hoc reviewer||External||International||2008||2012|
|Molecular and Biochemical Parasitology||Editorial Board||Member||External||National||2007|
|National Science Foundation (NSF)||Study Section||Ad hoc reviewer||External||National||2006||2006|
|NIH MIDRC (microbiology and infectious diseases research committee)||Study Section||Ad hoc reviewer||External||National||2006||2006|
|NIH PTHE (pathogenic eukaryotes)||Study Section||Member||External||National||2006||2010|
|American Society for Microbiology (ASM)||Professional/Scientific Organization||Member||External||National||2005|
|NIH PTHE (pathogenic eukaryotes) study section||Study Section||Ad hoc reviewer||External||National||2004||2006|
|German Society for Protozoology||Professional/Scientific Organization||Member||External||National||1996||2002|
|German Society for Parasitology (DGP)||Professional/Scientific Organization||Member||External||National||1996|
We are interested in the mechanisms of gene expression found in the unicellular eukaryote Trypanosoma brucei. This parasite is transmitted by tsetse in sub-Saharan Africa and causes the lethal Sleeping Sickness in humans. The few drugs used to treat the disease are toxic, expensive, and/or not effective for all parasite strains and stages of the disease. In addition, parasite resistance to these drugs is on the rise. Thus, identification of novel drug targets is a primary goal. In addition, we believe that long-term control of this pathogen will benefit from knowledge of its highly divergent gene expression mechanisms.
T. brucei lives freely in the blood of its mammalian host using Antigenic Variation of its cell surface glycoprotein coat as a means to evade the mammalian immune system. The gene family encoding the major antigen is transcribed by RNA polymerase (pol) I in a mono-allelic fashion. This is unique because eukaryotes use RNA pol I exclusively for transcription of ribosomal DNA while all mRNA is synthesized by RNA pol II. Furthermore, T. brucei deviates from standard eukaryotic gene expression by transcribing its genes polycistronically. Individual mRNAs are then processed from precursor RNA by spliced leader (SL) trans splicing and polyadenylation. Since trans splicing is an essential maturation step for all mRNA and SL RNA, the SL donor, is consumed in the process, parasite growth crucially depends on a strong and continuous supply of SL RNA.
Currently we are pursuing the following projects in the laboratory: Supported by two NIH R01 grants we study the multifunctional RNA pol I system and RNA pol II-mediated transcription of SL RNA genes. In addition, we are interested in the trans spliceosome which transfers the SL to mRNAs. We recently identified a cyclin-dependent kinase (CDK) that is of central importance to SL RNA modification, the trans splicing process and, consequently, parasite viability. Since CDKs are suitable drug targets for a number of diseases including cancer, we are excited at the prospect of having identified a promising drug target in trypanosomes.
In our research we employ a vast spectrum of methods in genetics, biochemistry and cell biology. We have particular strengths in proteomics (protein complex characterization by tandem affinity purification), in vitro transcription analysis, and genetic modification of trypanosomes that includes conditional gene silencing by RNAi. We have also entered realm of next generation sequencing by employing the ChIP-seq of transcription factors.
Accepting Lab Rotation Students: Summer '19, Fall '19, Spring '20
Lab Rotation Projects
Learn how to characterize a protein complex. We focus on transcription factors and the spliceosome of the eukaryotic human pathogen and model organism Trypanosoma brucei. We try to understand the mechanistic differences in gene expression between trypanosomes and their human hosts. This project involves in vivo tagging of a protein, tandem affinity purification, and a genetic analysis of the genes involved.
Dissect the CRK9 kinase enzyme complex, a promising chemotherapeutic target. CRK9 is essential for trypanosome gene expression and consists of three subunits. This project involves expression of recombinant subunits in wheat germ extract or insect cells and analysis of complex formation and kinase activity.