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Synthetische Hox-Gene

English title Synthetic Hox Genes
Applicant Gehring Walter
Number 125224
Funding scheme Project funding (Div. I-III)
Research institution Abteilung Zellbiologie Biozentrum Universität Basel
Institution of higher education University of Basel - BS
Main discipline Embryology, Developmental Biology
Start/End 01.07.2009 - 30.06.2012
Approved amount 308'941.00
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All Disciplines (2)

Discipline
Embryology, Developmental Biology
Molecular Biology

Keywords (5)

Synthetic Hox genes; Protein transduction; Single Molecule Imaging; Fluorescence Cross-Correlation Spectroscopy; Hox genes

Lay Summary (English)

Lead
Lay summary
We have constructed synthetic Drosophila Hoxgenes for Antennapedia and Sexcombs reduced , which are capable of inducing homeotic transformations in transgenic flies.These include antenna-to-leg transformations and the formation of an additional pair of salivary glands in the head region. These synthetic genes encode relatively short peptides of some 100 amino acids and comprise the homeodomain and the YPWM motif which are essential for function. Sex combs reduced (Scr) is the mastercontrol gene for salivary gland formation. Therefore, we have used a synthetic Sexcombs reduced( Scr) gene fused to Green Fluorescent Protein (GFP) as a probe for single molecule imaging and Fluorescence Correlation Specctroscopy (FCS) in live salivary gland cells. By using advanced imaging methods we can detect single GFP molecules and find out how a single transcriptionfactor molecule can find its target genes among some 18 000 genes in the entire genome. We have shown, that this is merely a stochastic process: the synthetic transcriptionfactors find their specific target sites by multiple association/dissociation events. The dissociation constant for the non-specific DNA-SCR complexes is rather low in the micromolar range, whereas the specific DNA-SCR complexes are in the nanomolar range, i.e. much more stable. These are the first estimated binding constants of transcriptionfactors measured in live cell nuclei.In the current project, we are extending these studies to specific target genes. Furthermore, we are attempting to use these synthetic peptides for inducing homeotic transformations by attaching so-called penetratin peptides to them which should allow them to penetrate into cells. This might have important medical applications , since penetrating peptides may be used as drugs.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Latin-american Society for Developmental Biology 29.02.2012 Montevideo Uruguay
Gordon Research Conference "Photosensory Receptors and Signal Transduction 22.01.2012 Galveston USA


Knowledge transfer events

Active participation

Title Type of contribution Date Place Persons involved
Kulturpalette Therwil 10.06.2012 Therwil, BL


Communication with the public

Communication Title Media Place Year
Talks/events/exhibitions Interview Kultur Palette Therwil German-speaking Switzerland

Awards

Title Year
Grosses Verdienstkreuz der Bundesrep Deutschland 2010

Associated projects

Number Title Start Funding scheme
109753 The Genetic Control of Development and Evolution by Hox and Pax Genes 01.10.2005 Project funding (Div. I-III)

Abstract

Hox-gene sind Masterkontrollgene, die den Bauplan der Tiere bestimmen.Wir haben synthetische Hox-Gene konstruiert, die nur für die Homeodomäne und das kleine YPWM-Motiv kodieren, insgesamt ca 80 Aminosäuren.Diese Transkriptionsfaktoren steuern hunderte von Zielgenen und vermögen in 100% aller transgenen Fliegen die Antennen in Tarsen (Füsse) zu transformieren. Wir verfolgen diese Transkriptionsfaktoren als fluoreszierende Einzelmoleküle vom Cytoplasma bis zu ihren Zielgenen im Zellkern. Dazu benutzen wir ein neu entwickeltes konfocales Laserraster- Mikroskop.Ausserdem versuchen wir die Transkriptionsfaktoren durch Fusion mit Penetratin-Peptiden in die Zellen einzuschleusen, um diese umzuprogrammieren.
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