When Cells Divide
If scientists could watch the birth of chromosomes and change the way they develop, they would be on the threshold of mind-boggling breakthroughs in treatments for many diseases, including genetic disorders. A team of researchers at the University of Dundee is not only “filming” the moment when new cells are born, but analysing all of the data produced by the pictures to understand what’s really going on…
The pictures look like psychedelic jellyfish swimming around in a tropical sea, but this is not Blue Planet, it’s a film of mitosis – the moment when a cell divides to form a pair of duplicates.
An art gallery in California has exhibited some of the Miro-like images, but despite their aesthetic appeal, they could be a significant step forward on the road to new treatments for cancer, brain damage or spinal injuries – plus many other medical problems.
“If we can illuminate the mechanisms of cell division,” says Dr Jason Swedlow, “at the mechanical and the molecular level, and at the level of tissue biology, that would be critical to understanding how cells work – how they integrate and make decisions.”
When cells divide, they make a ‘fate choice,’ ‘deciding’ what to become. The cells in tissues of the sort the Swedlow Laboratory is studying ‘choose’ to become neurons or not. Swedlow and his team are trying to determine which ones become neurons, and when. Then they put the film in reverse, enabling them to trace the cell all the way back to the source – and observe every other event that has happened since ‘birth’.
The problem is that in order to observe ‘neurogenesis’, you have to film thousands of other cells in action, as they divide and duplicate, and the data generated in the process adds up to many terabytes (a terabyte is a million million bytes), which then has to be analysed before you find the ‘needle in a haystack.’ And even though the Swedlow Lab (located in the Wellcome Trust Biocentre at the University of Dundee) has access to as much computing power as a bank, this is a difficult challenge.
The breakthrough tool that Swedlow and his team are working on now is a smart piece of software – a relational database management system (RDMS) and an open-source application developed by the Open Microscopy Environment (OME), an international consortium which Swedlow helped to found in 2000. OME builds software tools to manage and analyse the vast amounts of imaging data collected by academic and pharmaceutical labs round the world – for example, the data produced by digital fluorescence imaging, which marks or bleaches targets under the microscope so that observers can calculate what’s going on at microscopic level, including processes like molecular localisation, interaction and mobility.
The OME software can be downloaded free from the OME website (http://openmicroscopy.org), under the GNU General Public License, which allows re-distribution and resale, as long as the opensource nature of the source code is maintained. What motivates Swedlow himself is the ability to provide informatics solutions to the biology community at large, so scientists can make more rapid progress with experiments, including drug discovery and therapy development.
One of Swedlow’s objectives is to make data analysis a more routine procedure, via the convergence of several disciplines, including informatics and biology, and developing new imaging technology to “fine-tune and understand the role of phospho-specific reporters.”
The eureka moment was to capture a film of the instant a neuron was born
In other words, instead of being armchair researchers who gaze in amazement as cells reproduce, Swedlow and his team of 13 programmers and post-doctoral assistants try to make sense of what they see under the microscope, translating raw images into meaningful quantitative data which explains how cells divide.
Another key activity is to ‘perturb’ the whole process, intervening in various ways to test what happens when we manipulate cells – ultimately to develop pharmaceuticals and other treatments.
“We are very good at acquiring the images,” Swedlow explains, “but data management and data analysis turn the images into results which will help to solve problems, and that is where OME gives us the edge.”
In partnership with the University of Dundee’s Department of Applied Computing, Swedlow has also been working to improve the usability of OME, with usability specialists working directly with the user community and passing on feedback which Swedlow’s team of developers can use for new features.
So the Swedlow Laboratory combines expertise in cell biology, imaging and software to examine how cells progress through mitosis, and in partnership with Dr Kate Storey, also based in Dundee, to study neurogenesis.
For Swedlow and Storey, supported by their postdoctorate researcher, Arwen Wilcock, the eureka moment was to capture a film of the instant a neuron was born, by observing cell division in the embryos of chickens. “No-one has ever been able to see this before,” says Swedlow, explaining that the project has so far generated 2.5 terabytes of data over the last four years, documenting the magical moment of the birth of a neuron.
In the process, Swedlow’s team has also made significant advances in imaging methods, as well as data management and processing – new improved tools and techniques which will help future projects, in Scotland and beyond.
The Swedlow Laboratory is funded by the Wellcome Trust, Cancer Research UK, the Biotechnology and Biological Sciences Research Council (BBSRC) and the Engineering and Physical Sciences Research Council (EPSRC). The tools it has developed are already widely used by an increasing number of researchers worldwide, enabling future breakthroughs in biology and medicine even Swedlow and his sponsors can’t imagine