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Engineering gene networks on magnetic beads.
 
 

Gene Network Engineering - Isalan Group Homepage

Group Leader:



2000 PhD in Molecular Biology, University of Cambridge, UK. PhD thesis: "Selection of zinc fingers with novel DNA-binding specificities."

Postdoctoral positions at Gendaq Ltd, UK (now owned by Sangamo Biosciences, Richmond CA)

Postdoctoral positions at EMBL Heidelberg, Germany.

Summary
Group Overview:
We are interested in engineering synthetic gene networks to control gene expression in cells and to construct self-organising patterns, analogous to those used by organisms in morphogenesis and development. By building artificial gene networks, we hope to find the 'design principles' underlying why certain networks form particular structures or functions. A number techniques are used to achieve these aims:

(i) Protein engineering – to apply combinatorial and design approaches for constructing novel gene network components, such as our method for building customised zinc fingers to bind any desired DNA sequence (Nature Biotechnology 19, 656-60, 2001).

(ii)  Computer modelling and network analysis - to test gene network hypotheses. Recently, we published two essays comparing gene networks to self-referential arguments in ancient Greek philosophy (Nature 458:969, 2009; Bioessays 31(10):1110-5, 2009). These essays explain intuitively how a fish might make stripe patterns, and why static network arrow diagrams are dangerous.

(iii) Synthetic Gene Network construction - to obtain desired patterns or behaviours of gene expression. For example, we built an in vitro activator-repressor gene network to read synthetic morphogen gradients  (PLoS Biology 3(3), e64, 2005). More recently, we asked the question, "What happens when you add lots of new connections to an existing large gene network?". By shuffling E. coli transcription networks with promoter-ORF fusions we were able to see how tolerant the networks are to rewiring (Nature 452:840-5, 2008). 

(iv) Localised transfection - we have developed a way of targeting DNA, containing gene network constructs, to locations within a cell population. Cells can thus be transfected to micrometer resolution using magnetic beads (Nature Methods 2: 113-118,2005). 

 

 

Links to our Partners and Funding Agencies:

European Research Council (ERC): ERC Starting Grant
The Netsensor consortium: http://netsensor.embl.de/
The Zinc Finger Consortium: http://www.zincfingers.org/
Sysbionetwork.org: sysbionetwork.org
EMBL/CRG Partnership: EMBL/CRG Partnership
Google Scholar: Profile

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Research Lines
Selected Publications

Isalan M., Morrison M.
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Nature 458:969 (2009). PubMed ID: 19396124.abstract
Isalan M, Lemerle C, Michalodimitrakis K, Horn C, Beltrao P, Raineri E, Garriga-Canut M, Serrano L.
Evolvability and hierarchy in rewired bacterial gene networks
Nature 452(7189):840-5 (2008). PubMed ID: 18421347.abstract
Mark Isalan.
Zinc-finger nucleases: how to play two good hands
Nature Methods (2011). PubMed ID: 22205514.
Constante M, Grünberg R, Isalan M..
A biobrick library for cloning custom eukaryotic plasmids
PLoS One 6(8):e23685. Epub 2011 Aug 25 (2011). PubMed ID: 21901127.abstract
Herrmann F, Garriga-Canut M, Baumstark R, Fajardo-Sanchez E, Cotterell, J. et al.
p53 Gene Repair with Zinc Finger Nucleases Optimised by Yeast 1-Hybrid/ and Validated by Solexa Sequencing
PLoS One e20913. Epub 2011 Jun 9 (2011). PubMed ID: 21695267.

 
 
 

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