Wednesday, November 21, 2007

“In 10 years we could be creating artificial miniorgans”

This is an article that I published in the PRBB monthly journal “el•lipse”. It explains what Mark Isalan, a group leader at the CRG, is doing (as I promised in my last entry).


To generate artificial life might not be as much science-fiction as we may think. The gene network engineering group, from the systems biology program at the CRG, is already making small steps towards that goal. The six people who work under the direction of Briton Mark Isalan – and who represent five different nationalities – have spent the last year working in several projects that will eventually make it possible to create an artificial miniorgan (say, a gland). This miniorgan, which would have some functionality and which could in the future have some clinical application, could exist in less than 10 years, says Isalan.

But for the moment, the daily task of the group is working out the basics. The group focuses on three main lines of research. One is protein engineering – constructing proteins with new properties - and in particular engineering customised zinc fingers (a type of molecular structure able to bind DNA) so that they can bind any desired DNA sequence. One of Isalan’s main scientific contributions so far was actually being part of the team who discovered the protein-DNA recognition code for Zinc fingers, i.e. which aminoacids recognise which nucleotides. This code has been essential for the posterior zinc finger engineering. The second line of research of the group is synthetic gene network construction, which consists on joining together carefully selected genes and regulatory sequences in order to construct artificial 'circuits' that can sense particular conditions or signals within a cell, and respond accordingly – just as electrical circuits do. Finally, the group has developed a new way of delivering DNA containing gene network constructs to specific locations within a mammalian cell population. With this technique, which is called PCR bead transfection and uses magnetic beads, they can transfer a specific DNA construct to a single selected cell within a population. The group, formed only by biologists, also uses the help of some computer scientists at other groups at the PRBB, such as Ricard Solé (GRIB), Luis Serrano (CRG) and James Sharpe (CRG), to do some computer modelling and test their network hypotheses.

By combining these lines of research, the group intends to achieve several aims. Scientifically, their work should help finding out the ‘design principles’ underlying complex biological systems, such as the development of an organism, the formation of the stripes present in some animals, etc. by artificially re-creating the pathways involved in these processes. But their work also has more practical applications. For example, they are working on a biotechnology application of their engineered networks within the EU project Netsensor, in collaboration with Luis Serrano and other European groups. This project consists on introducing into cells a construct that will correct a carcinogenic mutation only if it senses that this is needed. The construct carries an artificial sensor gene network, and a customized Zinc finger nuclease to cut and repair the p53 gene, a gene usually affected in cancer.

“The p53 nuclease Zinc finger is my favourite result so far; we engineered this enzyme to do something we couldn’t do before”, says Isalan of his discoveries since he joined the CRG, a year ago. This is one little step towards what would be Isalan’s dream: to cure a disease using one of these gene networks. Again, optimistically, he thinks we’ll only have to wait a decade.

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