Movies for the human genome
At its outset, one aim of the Human Genome Project was to identify all the genes in the human genome, so as to enable systematic approaches to understanding gene function. Today, a decade on from the human draft sequence, a global scan of all 21,000 human genes identifies many ways that human genes are involved in cell biological processes such as cell division and migration - the basic stuff of life.
The data have been developed using the freely available human genome sequence: as with the public release of that sequence, the consortium that produced the current results has made them freely available to the research community.
The Mitocheck Consortium developed high-throughput systems to disrupt the working of each gene and to study the consequences for cell behaviour using time-lapse microscopy: this 'Candid Camera' of the cell caught how cells respond to gene disruption.
The team produced about 190,000 movies.
"This work is the fruit of an innovative European collaboration in functional genomics, bringing multiple large-scale experimental strategies to bear on a key component of basic biology: how cells manage the doubling of their DNA when they divide. Because of its scale it would not have been possible without new software and analysis tools."
Dr Richard Durbin, a researcher at the Wellcome Trust Sanger Institute
To carry out biology on this scale, the team developed automated systems to inhibit gene function and to study the effects on cell behaviour such as migration, division. The observations were supported by newly developed computer programmes to report the cell observations.
The team studied almost two billion cell nuclei.
Cell division is often poorly captured in studies of mutation, in part simply because it is such a short part of a cell's life. However this vital part of a cell's - and our - life is ideally captured by time-lapse microscopy. The study found almost 600 genes that could be involved in these basic functions.
The system uses reduction in gene activity caused by siRNAs - small, interfering RNAs designed to match and thus interfere with the sequence of one specific gene. The elegant high throughput platform that EMBL scientists developed to silence all of an organism's genes in a fast and systematic manner is itself proving a boon to the scientific community.
"A year after we developed these new siRNA microarrays they're already in use by over 10 research groups from across Europe."
Dr Rainer Pepperkok, who led the method's development at EMBL
The team have yet to uncover exactly how these genes act at the molecular level - a task which will be tackled by a follow-up project called MitoSys. All data from this follow-up work will also be made freely available online, creating what Professor Ellenberg describes as a 'one-stop-shop' for mitosis research.
"Without mitosis, nothing happens in life, really and when mitosis goes wrong, you get defects like cancer."
Jan Ellenberg, who led the study at EMBL