UCONN

HEALTH

Photo of Arthur  Günzl, Ph.D.

Arthur Günzl, Ph.D.

Professor, Genetics and Genome Sciences
Academic Office Location:
Genetics and Genome Sciences
UConn School of Medicine
263 Farmington Avenue
Farmington, CT 06030
Phone: 860-679-8878
Fax: 860 679-8345
Email: gunzl@uchc.edu
Website(s):

Genetics & Developmental Biology Graduate Program

Molecular Biology & Biochemistry Graduate Program

Education
DegreeInstitutionMajor
M.S.University of Tübingen and Duke UniversityBiological Sciences
Ph.D.University of TübingenMPI Biological Sciences

Post-Graduate Training
TrainingInstitutionSpecialty
FellowshipGerman Academic Exchange Service (DAAD) Graduate Student Fellowship
PostdoctoralMax-Planck-Institute for Molecular GeneticsPost-doctoral Fellow under Dr Albrecht Bindereif
PostdoctoralYale University School of MedicinePost-doctoral Fellow under Dr. Elisabetta Ullu and Dr. Christian Tschudi
FellowshipExcellence in the Life Sciences (EMBO), GermanyEMBO long term fellowship
Name & DescriptionCategoryRoleTypeScopeStart YearEnd Year
The NIH IDMR02 Special Emphasis Review PanelStudy SectionAd hoc reviewerExternalNational20122012
the NIH IDM-M (Eukaryotic Pathogens and Vectors) Study SectionAd hoc reviewer ExternalNational20122012
the NIH TMRC (tropical medicine research centers) study section Study SectionAd hoc reviewer ExternalNational20112011
the NIH ZRG1 IDM-R Special Emphasis Review Panel Study SectionAd hoc reviewer ExternalNational20102010
the NIH ZRG1 IDM-B Special Emphasis Review Panel Study SectionAd hoc reviewer ExternalNational20102010
Eukaryotic Cell Editorial BoardMemberExternalNational20102012
New England Association of ParasitologistsProfessional/Scientific OrganizationMemberExternalRegional2009
Molecular and Biochemical ParasitologyStudy SectionAd hoc reviewer ExternalInternational20082012
the Wellcome Trust, UKStudy SectionAd hoc reviewer ExternalInternational20082012
the Ohio Cancer SocietyStudy SectionAd hoc reviewer ExternalNational20082012
the US-Israel Binational Science FoundationStudy SectionAd hoc reviewer ExternalInternational20082012
Molecular and Biochemical ParasitologyEditorial BoardMemberExternalNational2007
National Science Foundation (NSF)Study SectionAd hoc reviewer ExternalNational20062006
NIH MIDRC (microbiology and infectious diseases research committee) Study SectionAd hoc reviewer ExternalNational20062006
NIH PTHE (pathogenic eukaryotes) Study SectionMemberExternalNational20062010
American Society for Microbiology (ASM)Professional/Scientific OrganizationMemberExternalNational2005
NIH PTHE (pathogenic eukaryotes) study sectionStudy SectionAd hoc reviewer ExternalNational20042006
German Society for ProtozoologyProfessional/Scientific OrganizationMemberExternalNational19962002
German Society for Parasitology (DGP)Professional/Scientific OrganizationMemberExternalNational1996

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 '16, Fall '16, Spring '17


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.

Journal Articles

Book Chapters

  • Pre-mRNA splicing in Trypanosoma brucei: factors, mechanisms, and regulation
    Preußer C, Jaé N, Günzl A, Bindereif A RNA Metabolism in Trypanosomes Nucleic Acids and Molecular Biology 2012 Jan;49-77
  • RNA Polymerases and Transcription Factors of Trypanosomes
    Günzl A RNA Metabolism in Trypanosomes Nucleic Acids and Molecular Biology 2012 Jan;1-27
  • Transcription in trypanosomes: a different means to the end
    Günzl A, Vanhamme L, Myler PJ Trypanosomes – After the Genome 2007 Jan;

Letters

Reviews