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|
|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.
Accepting Lab Rotation Students: Summer 2022, Fall 2022, and Spring 2023
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.
A distinct complex of PRP19-related and trypanosomatid-specific proteins is required for pre-mRNA splicing in trypanosomes.
Nucleic acids research 2021 Dec;49(22):12929-12942
The large repertoire of 2'-O-methylation guided by C/D snoRNAs on Trypanosoma brucei rRNA.
RNA Biology 2020 Apr;171018-1039
Rapid block of pre-mRNA splicing by chemical inhibition of analog-sensitive CRK9 in Trypanosoma brucei.
Molecular Microbiology 2020 Feb;1131225-1239
An RNA polymerase II-associated TFIIF-like complex is indispensable for SL RNA gene transcription in Trypanosoma brucei.
Nucleic acids research 2018 Feb;461695-1709
Metacyclic VSG expression site promoters are recognized by the same general transcription factor that is required for RNA polymerase I transcription of bloodstream expression sites.
Molecular and biochemical parasitology 2017 Jul;21652-55
Cyclin-Dependent Kinase CRK9, Required for Spliced Leader trans Splicing of Pre-mRNA in Trypanosomes, Functions in a Complex with a New L-Type Cyclin and a Kinetoplastid-Specific Protein.
PLoS pathogens 2016 Mar;12(3):e1005498
The dynein light chain LC8 is required for RNA polymerase I-mediated transcription in Trypanosoma brucei, facilitating assembly and promoter binding of class I transcription factor A.
Molecular and Cellular Biology 2015 Oct;3695-107
The spliceosomal PRP19 complex of trypanosomes.
Molecular Microbiology 2014 Dec;95(5):885-901
Mono-allelic VSG expression by RNA polymerase I in Trypanosoma brucei: expression site control from both ends?
Gene 2014 Sep;556(1):68-73
A new strategy of RNA interference that targets heterologous sequences reveals CITFA1 as an essential component of class I transcription factor A in Trypanosoma brucei.
Eukaryotic Cell 2014 Apr;13(6):785-95
Phosphorylation of the TATA-binding protein activates the spliced leader silencing pathway in Trypanosoma brucei.
Science Signaling 2014 Jan;7(341):ra85
Promoter occupancy of the basal class I transcription factor A differs strongly between active and silent VSG expression sites in Trypanosoma brucei.
Nucleic Acids Research 2013 Dec;42(5):3164-76
Trypanosoma brucei harbours a divergent XPB helicase paralogue that is specialized in nucleotide excision repair and conserved among kinetoplastid organisms.
Molecular Microbiology 2013 Oct;90(6):1293-308
Trypanosome cdc2-related kinase 9 controls spliced leader RNA cap4 methylation and phosphorylation of RNA polymerase II subunit RPB1.
Molecular and Cellular Biology 2013 May;33(10):1965-75
MCM-BP is required for repression of life-cycle specific genes transcribed by RNA polymerase I in the mammalian infectious form of Trypanosoma brucei.
PloS one 2013 Jan;8(2):e57001
Characterization of a novel class I transcription factor A (CITFA) subunit that is indispensable for transcription by the multifunctional RNA polymerase I of Trypanosoma brucei.
Eukaryotic Cell 2012 Dec;11(12):1573-81
Development of an efficient in vitro transcription system for bloodstream form Trypanosoma brucei reveals life cycle-independent functionality of class I transcription factor A.
Molecular and Biochemical Parasitology 2012 Jan;181(1):29-36
Transcription by the multifunctional RNA polymerase I in Trypanosoma brucei functions independently of RPB7.
Molecular and biochemical parasitology 2011 Nov;180(1):35-42
A TFIIH-associated mediator head is a basal factor of small nuclear spliced leader RNA gene transcription in early-diverged trypanosomes.
Molecular and cellular biology 2010 Jan;30(23):5502-13
SMN-assisted assembly of snRNP-specific Sm cores in trypanosomes.
Genes & development 2009 Jul;23(14):1650-64
Spliceosomal proteomics in Trypanosoma brucei reveal new RNA splicing factors.
Eukaryotic cell 2009 Jul;8(7):990-1000
Transcriptionally active TFIIH of the early-diverged eukaryote Trypanosoma brucei harbors two novel core subunits but not a cyclin-activating kinase complex.
Nucleic acids research 2009 Jun;37(11):3811-20
Tandem affinity purification of proteins.
Current protocols in protein science / editorial board, John E. Coligan ... [et al.] 2009 Feb;Chapter 19(SUPPL. 55):Unit 19.19
Identification of a novel chromosomal passenger complex and its unique localization during cytokinesis in Trypanosoma brucei.
PloS one 2008 Jan;3(6):e2354
Multifunctional class I transcription in Trypanosoma brucei depends on a novel protein complex.
The EMBO Journal 2007 Nov;26(23):4856-66
Active RNA polymerase I of Trypanosoma brucei harbors a novel subunit essential for transcription.
Molecular and cellular biology 2007 Sep;27(17):6254-63
Purification of components of the translation elongation factor complex of Plasmodium falciparum by tandem affinity purification.
Eukaryotic cell 2007 Apr;6(4):584-91
Spliced leader RNA gene transcription in Trypanosoma brucei requires transcription factor TFIIH.
Eukaryotic cell 2007 Apr;6(4):641-9
alpha-tubulin minichromosome promoters in the stichotrichous ciliate Stylonychia lemnae.
Eukaryotic cell 2007 Jan;6(1):28-36
Antimalarial activity of the anticancer and proteasome inhibitor bortezomib and its analog ZL3B.
BMC clinical pharmacology 2007 Jan;713
Pre-mRNA splicing in Trypanosoma brucei: factors, mechanisms, and regulation
RNA Metabolism in Trypanosomes Nucleic Acids and Molecular Biology 2012 Jan;49-77
RNA Polymerases and Transcription Factors of Trypanosomes
RNA Metabolism in Trypanosomes Nucleic Acids and Molecular Biology 2012 Jan;1-27
Transcription in trypanosomes: a different means to the end
Trypanosomes – After the Genome 2007 Jan;
Response to "Role of RPB7 in RNA pol I transcription in Trypanosoma brucei".
Molecular and biochemical parasitology 2011 Nov;180(1):45-6
The pre-mRNA splicing machinery of trypanosomes: complex or simplified?
Eukaryotic cell 2010 Aug;9(8):1159-70
|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)|