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Conlan Lab
Mechanisms of Transcription in Plants and Yeast 


 


Research Team

Steve Conlan

Deyarina Gonzalez

Adam Bowen

Nurul Hamidi

Jim Young

 

Research
Funding

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Associated
Degree Schemes

Genetics BSc

Medical Genetics BSc


Dr. Steve Conlan, e-mail r.s.conlan@swan.ac.uk

Research Focus
The research focus of my group is in understanding the molecular mechanisms underlying the repression of gene transcription in eukaryotes, and how this may be applied to areas including plant biotechnology and biomedicine.
Transcription repression is emerging as a key regulatory strategy for both animals and plants to prevent crucial regulatory proteins from being expressed in inappropriate temporal or spatial domains. Repression is a dynamic process that regulates gene expression at two points. First, a gene can be repressed but primed for transcription, de-repression resulting in rapid upregulation of expression.  Second, expression of an actively transcribed gene can be downregulated rapidly. Repression occurs through two distinct yet overlapping mechanisms: the stabilization of nucleosomes on DNA to form a closed chromatin structure and the inactivation of the transcription machinery. Research is undertaken in two model systems, the yeast Saccharomyces cerevisiae and the higher plant Arabidopsis thaliana. Specifically my research focuses on the analysis of macro-molecular transcription complexes using advanced proteomics approaches, and transcriptomic/proteomic approaches to identify and analyse co-regulated gene clusters.

Plant Research
Plant research involves characterising known developmental determinants, as well as novel plant proteins, that appear to be analogous to co-repressor proteins from other eukaryotic systems. The study of transcription mechanisms, beyond DNA binding proteins, is an emerging field in plant research. It offers the opportunity of confirming the existence of conserved eukaryotic regulatory mechanisms along with the promise of uncovering novel plant regulatory mechanisms. In turn these mechanisms will permit a greater understanding of aspects of plant development and environmental response. In addition understanding these mechanisms may lead to the development of ‘pathway repression’ – the targeting of specific biochemical pathways for up/down regulation. We are studying the Arabidopsis transcriptional regulator LEUNIG. Through characterising the molecular mechanisms employed by LEUNIG to repress transcription using advanced proteomic approaches we aim characterise the important role that this regulator appears to play in many aspects of signal perception and development in higher plants. We are also studying a novel class of plant transcription regulators in Arabidopsis, which function as transcription repressors, and may have a role in early plant development.

Yeast Research Research into novel mechanisms of repression uses the simple and powerful genetic system of S. cerevisiae to define molecular mechanisms that are likely to be conserved between model and infectious yeast, and higher eukaryotes.

Disease mechanisms Many studies into Human diseases (e.g. some cancers) are currently identifying transcription co-repressors as potential causative agents due to either enhanced or suppressed function. Due to the complex genetics of humans and lack of appropriate cell lines these studies in human tissue or mammalian models are not able to uncover specific mechanisms of co-repressor malfunction. Our research investigating co-repressors aims to elucidate specific mechanisms which can then be taken through to studies in mammalian systems. Specifically we are interested in the mechanisms of repression regulating transcription per se.

Fungal Infection We are investigating the role of co-repressors in the regulation of cell adherence. We are characterising the composition, mechanism and temporal/spatial aspects of a co-repressor mediated cell surface glycoprotein adhesion regulatory pathway. In collaboration with the scientists in Swansea’s nanotechnology centre we are using atomic force microscopy to measure the effects on cell-substrate adhesion resulting from genetic modifications made to components of transcription repression complexes. The long term objectives of this research are to translate the understanding of the molecular mechanisms and bio-mechanics of cell adhesion to both medical and agricultural systems. In medicine the adhesion of fungal pathogens to host tissue and also to inert surfaces such as prosthetic devices (e.g. catheters) has recently been recognized as playing a significant role in human infection, as has the increased susceptibility of immuno-compromised patients to fungal infection.

Recent publications: Yeast Transcription
R. Steven Conlan
and Dimitris Tzamarias (2001). Sfl1 functions via the corepressor Ssn6-Tup1 and the cAMP-dependent protein kinase Tpk2. J. Mol. Biol. 309 (5) 1007-1015

R. Steven Conlan, Niki Gounalaki, Pantelis Hatzis, and Dimitris Tzamarias (1999). The Tup1-Cyc8 protein complex can shift from a transcriptional co-repressor to a transcription co-activator J. Biol. Chem. 274(1) 205-210

Manolis Papamichos-Chronakis, R. Steven Conlan, Niki Gounalaki, Tijana Copf, and Dimitris Tzamarias (2000). Hrs1/Med3 is a Cyc8-Tup1 corepressor target in the RNA polymerase II holoenzyme. J Biol Chem. 275(12):8397-403

Recent publications: Plant Transcription
Vaniyambadi V. Sridhar, Anandkumar Surendrarao, Deyarina Gonzalez, R. Steven Conlan, and Zhongchi Liu (2004). Transcriptional repression of target genes by LEUNIG and SEUSS, two interacting regulatory proteins for Arabidopsis flower development. Proc. Natl. Acad. Sci. 101(31):11494-9.

R. Steven Conlan, Michael Hammond-Kosack, and Michael Bevan (1999). Transcription activation mediated by the bZIP factor SPA on the endosperm box is modulated by ESBF-1 in vitro. Plant J. 19 (2) 173-181.

Leo Galweiler, R. Steven Conlan, Patricia Mader, Jeff Schell, Klaus Palme, and Ian Moore (2000) DNA binding by Gal4 is sensitive to methylation of its binding site in plant chromatin. Plant J. 23(1) 143-157.

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University of Wales Swansea

©2003 Molecular Biology Research Group, UW Swansea.