Re: [GRG] Computational Biology

Contact: Britta Schlüter
britta.schlueter@uni.lu
352-466-644-6563
University of Luxembourg

Computational biology: Cells reprogrammed on the computer
Scientists at the Luxembourg Centre for Systems Biomedicine (LCSB)
of the University of Luxembourg have developed a model that makes
predictions from which differentiated cells – for instance skin
cells – can be very efficiently changed into completely different
cell types – such as nerve cells, for example. This can be done
entirely without stem cells. These computer-based instructions for
reprogramming cells are of huge significance for regenerative
medicine. The LCSB researchers present their results today in the
prestigious scientific journal Stem Cells.

This is the first paper based solely on theoretical, yet
practically proven, results of computational biology to be
published in this journal. (DOI: 10.1002/stem.1473).

All cells of an organism originate from embryonic stem cells, which
divide and increasingly differentiate as they do so. The ensuing
tissue cells remain in a stable state; a skin cell does not
spontaneously change into a nerve cell or heart muscle cell. “Yet
the medical profession is greatly interested in such changes,
nonetheless. They could yield new options for regenerative
medicine,” says Professor Antonio del Sol, head of the
Computational Biology group at LCSB. The applications could be of
enormous benefit: When nerve tissue becomes diseased, for example,
then doctors could take healthy cells from the patient’s own skin.
They could then reprogram these to develop into nerve cells. These
healthy nerve cells would then be implanted into the diseased
tissue or even replace it entirely. This would treat, and ideally
heal, diseases such as Parkinson’s disease.

The techniques for cell programming are still in their infancy.
Stem cell researchers Shinya Yamanaka and John Burdon received the
Nobel Prize for converting differentiated body cells back into stem
cells only last year. The first successful direct conversion of
skin cells to nerve cells in the lab was in 2010. Biologists add
refined cocktails of molecules, i.e. growth factors, to the cell
cultures in a certain order. This allows them to control the
genetic activity in the conversion process. However, this method so
far has been largely guided by – educated – trial and error.

Variable jumping between different cell lines is possible

Now, the LCSB researchers have replaced trial and error with
computer calculations, as computer scientist and PhD student at
LCSB Isaac Crespo explains: “Our theoretical model first queries
databases where vast amounts of information on gene actions and
their effects are stored and then identifies the genes that
maintain the stability of differentiated cells. Working from the
appropriate records, the model suggests which genes in the starting
cells need to be switched on and off again, and when, in order to
change them into a different cell type.”

“Our predictions have proved very accurate in the lab,” says
Professor del Sol: “And it turns out it makes no difference at all
how similar the cells are. The models work equally well for cell
lines that have only just branched off from one another as for
those that are already very far apart.” Prof. del Sol’s and
Crespo’s model thus allows highly variable jumping between very
different cell types without taking a detour via stem cells.

The biologists and medical scientists still have their lab work cut
out for them: They have to identify all the growth factors that
initiate the respective genetic activities in the correct,
predicted order.