|
Faculty
Arthur Günzl
Associate Professor, Center for Microbial Pathogenesis
gunzl@uchc.edu
Areas of Interest:
Trypanosomatids are unicellular, flagellated eukaryotes and a group
of nature’s most versatile parasites infecting all kinds of vertebrates,
insects and even plants. Some of these organisms cause major human
diseases such as African sleeping sickness (Trypanosoma brucei),
Leishmaniases (Leishmania spp.), and Chagas’ disease (Trypanosoma
cruzi). Worldwide more than 500 million people are at risk to be
infected by these parasites, and together they account for 150,000
reported deaths and more than 2 million new clinical cases each year
(WHO, www.who.int./tdr).
Drugs for these diseases are few and toxic, and parasite resistance is
on the rise. Therefore, it becomes increasingly important to develop new
therapeutic strategies.
We are interested in these parasites’ mechanisms of gene expression and
focus on the identification and functional characterization of essential
factors or factor domains in the hope to find parasite-specific targets.
We work with T. brucei and our projects address aspects which are
specific to this parasite (multifunctional RNA polymerase I
transcription) and characteristics which are shared by this group of
parasites (spliced leader RNA synthesis).
We employ various methods in cell biology, genetics and biochemistry
including conditional gene expression silencing by RNA interference.
Moreover, we have recently developed useful functional in vitro
assay systems and a modified tandem affinity purification protocol for
proteins which is based on a novel epitope combination. Together these
methods are efficient means to identify and functionally characterize
parasite proteins.
Lab rotation projects:
1) Characterize candidate transcription or trans splicing factors.
This project involves epitope tagging of a candidate factor,
purification of the factor to homogeneity, and a functional analysis of
the factor conducted in vivo and in vitro.
2) Analyzing transcription termination. This projects involves
the generation and mutation of constructs for transcription assays to
determine the sequence element which terminates transcription of the
parasite’s (unique) multifunctional RNA polymerase I.
Selected Publications:
Takebe, S, WH Witola, B Schimanski, A Günzl and C Ben Mamoun (2007).
Purification of components of the translation elongation factor complex
of Plasmodium falciparum by tandem affinity purification. Eukaryot Cell,
6, in press
Lee, JH, TN Nguyen, B Schimanski and A Günzl (2007). SL RNA gene
transcription in Trypanosoma brucei requires transcription factor TFIIH.
Eukaryot Cell 6, in press
Günzl, A, L Vanhamme and PJ Myler (2007). Transcription in trypanosomes:
a different means to the end. In Trypanosomes – After the Genome. Eds. D
Barry, J Mottram, R McCulloch and A Acosta-Serrano. Horizon Press,
Pittsburgh, USA, in press
Skovorodkin, I, A Pimenov, I Raykhel, B Schimanski, D Ammermann and A
Günzl (2007). Analysis of -tubulin minichromosome promoters in the
stichotrichous ciliate Stylonychia lemnae. Eukaryot Cell 6, 28-36
Nguyen, TN, B Schimanski, A Zahn, B Klumpp and A Günzl (2006).
Purification of an eight subunit RNA polymerase I complex in Trypanosoma
brucei. Mol Biochem Parasitol 149, 27-37
Schimanski, B, J Brandenburg, TN Nguyen, MJ Caimano and A Günzl (2006).
A TFIIB-like protein is indispensable for spliced leader RNA gene
transcription in Trypanosoma brucei. Nucleic Acids Res 34, 1676-1684
Schimanski, B, TN Nguyen and A. Günzl (2005). Highly efficient tandem
affinity purification of trypanosome protein complexes based on a novel
epitope combination. Eukaryot Cell 4, 1942-1950
Schimanski, B, TN Nguyen and A Günzl (2005). Characterization of a
multi-subunit transcription factor complex essential for SL RNA gene
transcription in Trypanosoma brucei. Mol Cell Biol 25, 7303-7313
Palfi, Z, B Schimanski, A Günzl, S Lücke and A Bindereif (2005). U1
small nuclear RNP from Trypanosoma brucei: a minimal U1 snRNA with
unusual protein components. Nucleic Acids Res 33, 2493-2503
Schimanski, B, G Laufer, L Gontcharova, and A Günzl (2004). The
Trypanosoma brucei spliced leader RNA and rRNA gene promoters have
interchangeable TbSNAP50-binding elements. Nucleic Acids Res 32,
700-709.
Günzl, A, T Bruderer, G Laufer, B Schimanski, L-C Tu, H-M Chung, and
MG-S Lee (2003). RNA polymerase I transcribes procyclin genes and
variant surface glycoprotein gene expression sites in Trypanosoma brucei.
Eukaryot Cell 2, 542-551.
Schimanski, B, B Klumpp, G Laufer, RJ Marhöfer, P Selzer, and A Günzl
(2003). The second largest subunit of Trypanosoma brucei’s
multifunctional RNA polymerase I has a unique N-terminal extension
domain. Mol Biochem Parasitol 126, 193-200.
Günzl, A (2003). Transcription. In Molecular and Medical Parasitology.
Eds J.Marr, T. Nilsen, and R. Komuniecki. Academic Press, London, UK,
pages 47-65.
|
