A study that could point the way towards the development of cures for Parkinson's, Alzheimer's, liver disease and diabetes has been published by a team that includes three researchers from King Abdullah University of Science and Technology (KAUST). The group of systems biologists and engineers employed innovative techniques to study transcription factors (TFs), proteins that play a crucial role in tissue development by orchestrating the transcriptional networks underlining this tightly controlled process. Combinatorial interaction among TFs results in the differentiation of different types of tissue – for example combinations lead to the differentiation of muscle tissue or brain tissue.

The genetic template for each tissue type is contained in DNA, and the TFs control the transfer – or transcription – of this information by binding with specific sequences of DNA.

The process by which this information is used to create different types of cell is known as tissue-specific gene expression, and the way that TFs combine to control this process is known as combinatorial regulation.

The research team has compiled the first catalogue of TF combinations in mice and men, identifying networks containing roughly 5,000 interactions between TFs. The two types of mammal were used to double-check the findings and eliminate misleading results known as false positives. And the team discovered that roughly half of the interactions between TFs that they observed were common to both mice and men.

Previous studies examined the behavior of individual TFs in isolation but the new report is the first to describe how they act when they combine. "The data highlight the importance of TF combinations for determining cell fate," says the report. "The availability of large TF combinatorial networks in both human and mouse will provide many opportunities to study gene regulation, tissue differentiation, and mammalian evolution."

The paper, An Atlas of Combinatorial Transcriptional Regulation in Mouse and Man, has been published as the cover article in the top-rated journal Cell. The lead author is Dr Timothy Ravasi, Principal Investigator at the Red Sea Laboratory of Integrative Systems Biology and Associate Professor of Bioengineering, who worked with post-doctoral fellow Carlo Vittorio Cannistraci and Vladimir Bajic, Director of the Computational Bioscience Research Center and Professor, Applied Mathematics and Computational Science.

The findings bring the use of stem cells to treat a range of degenerative diseases a step closer, according to Dr Ravasi.

"The power of the stem cell is that it can be differentiated into different types of tissue," he said. "People have tried to do this, but the problem is how you make it differentiate.

"Now we have made all the combinatorial networks available and if we're right then we can take TFs and express them in stem cells. Because we have mapped all these combinations, theoretically we can drive the stem cell to differentiate towards specific types of tissue.

"For example we mapped the network of TFs that is specific to brain tissue, so if you take this combination of TFs and make it express in stem cells theoretically you could drive the stem cell to differentiate into brain cells – and this could be used to cure Parkinson's. That is the concept – you could regenerate the brain or liver, all types of organs.

"Technically we can do it. For example you have a Parkinson's patient. We take the stem cell from the body, maybe from the bone marrow. Then we take the network of TFs that we believe can differentiate neural tissue and we put it into the stem cell and activate it, and if we've got it right the stem cell should differentiate into brain tissue. Then you take the brain tissue and inject it into the brain of the patient, and because the stem cells were taken from the patient there is no risk of rejection." The new brain cells would then divide and increase in number in the normal way, and the patient's condition would improve.

"It is not just the brain," added Dr Ravasi. "If you want to cure the pancreas you would inject pancreatic tissue, and so forth. With muscular dystrophy you would take the network that is specific to skeletal muscles and inject the resulting tissue. "All these types of disease are degenerative, the cell dies or cannot regenerate any more. With this stem cell therapy you could regenerate the cells as you liked. Dr Ravasi said the method could even be used to cure diabetes, which is a major scourge across Saudi Arabia and the rest of the Gulf region.

"With Type 1 diabetes the pancreatic Beta cells, which produce insulin, are dead and that's the reason you don't produce any more insulin yourself.

"Now if you can differentiate this cell and put it back into the pancreas you don't need to inject insulin any more because your cells will have started to produce insulin again."

The paper is the result of five years' study and the team employed advanced technical methods to carry out their work, including a robotic system that combined proteins much more quickly and accurately than any human scientist could.

The next step for Dr Ravasi and his colleagues is to expand the scope of the research to include five species from different stages of the evolutionary chain – reef-building coral, the fruit fly and sea urchins in addition to mice and men. This should provide insights into how the process of gene expression developed, which could prove invaluable for researchers engaged in genetic engineering.

A paper containing these latest findings is currently being written at KAUST and is due to be published in September. And the location of the university has proved a bonus – Dr Ravasi spent the morning of the day he was interviewed for this article collecting coral samples from the stretch of sea in front of the campus.