Education

Degree	Institution	Major
MS	University of Tübingen and Duke University	Biological Sciences
PhD	University of Tübingen	MPI Biological Sciences

Post-Graduate Training

Training	Institution	Specialty
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
NIH PTHE (pathogenic eukaryotes) study section 2/2022	Study Section	ad hoc reviewer	External	National	2022	2022
Israel Science Foundation	Other	reviewer	External	International	2020	2020
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	Professional/Scientific Journal	Editorial Board Member	External	National	2007	2021
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
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.

Not Accepting Lab Rotation Students at this time 

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.

Günzl

 

Journal Articles

Book Chapters

Erratums

Letters

Reviews

Title or Abstract	Type	Sponsor/Event	Date/Year	Location
The trypanosome pre-mRNA splicing machinery and its potential Achilles heel, the cyclin-dependent kinase CRK9	Other	The Ohio State University	2020	The Ohio State University, (Zoom)