HOW MUCH DARK MATTER IS IN MY BODY?
THE SECRET CHEMISTRY OF PROTEINS For years, scientists have been trying to get a handle on dark matter, the mysterious substance holding our universe together. Now new research has led to a stunning discovery: our bodies may also be dependent on their pow
Everyone knows that a caterpillar changes completely when it becomes a butterfly. However, paradoxically, it also stays the same. The process is probably the most dramatic transformation in the animal kingdom: limbs appear where there were none, while organs move throughout the body, mutating, disintegrating and being put back together again. They’re two creatures that couldn’t be more different, but the butterfly and caterpillar have an identical genome. How? What caused the caterpillar’s metamorphosis, if not its genetic blueprint?
The answer has astonished even experienced biologists. The change from caterpillar to butterfly is actually controlled by proteins. Proteins are polymer chains formed from amino acids and
are based on a blueprint in the DNA. All the body’s proteins link together to form the “proteome”.
In modern medicine, this is considered a dull area of study and is often overlooked. Proteins were researched a long time ago, their role in the body reduced to being a source of energy and building block for muscles, organs and the blood. But that was a big mistake because, in actual fact, proteins are the most active designers of life and implement our genetic makeup. Furthermore, there are 400,000 different proteins that affect every process in the body, making up 15% of our overall mass. They influence healing, communication between cells and the immune system. “Many people think that we’re controlled by our genes,” explains Professor Matthias Mann from the Max Planck Institute of Biochemistry. “But, in reality, it’s the proteins that do something in us and to us.”
The strange thing is that around 50% of these proteins are still completely unknown. They are a kind of dark matter in our bodies – and we’re only just beginning to understand the power they have over us.
HOW MANY SECRETS ARE HIDDEN IN THE BODY?
The role proteins play in the body is crucial, but it was long thought impossible to decode their powerful network. After all, a single cell can be controlled by up to 10,000 proteins. “Our proteome is probably a lot more complex than our genome,” explains Professor Mann. However, with the computing power now available, it’s finally possible to unscramble the complicated protein codes in the body and put them in a database. It’s a job for Dr Sean O’donoghue, data visualisation scientist at the Commonwealth Scientific and Industrial Research Organisation (CSIRO) in Sydney. For years, he and his team have been putting together gene maps to depict the cosmos of proteins in our body – and has stumbled across thousands of previously unknown chains. For the researchers, it’s like discovering human dark matter without having a clue what it actually does. “It may sound absurd, but we had to do two things,” explains Dr Andrea Schafferhans from the Technical University of Munich. “First we had to discover proteins we didn’t know were there, and then we had to find out why we didn’t know about them.” However, all that’s about to change.
DO PROTEINS HAVE A DARK SIDE?
For medicine, the discovery of dark matter in the body is both a blessing and a curse. On one hand, it could provide insights into protein-based illnesses like cancer and type 2 diabetes, neurodegenerative diseases such as Parkinson’s and Alzheimer’s, and it might also be a way of managing the ageing process. In other words it
“Dark proteins definitely have an important role, but we don’t know what it is yet.” ANDREA SCHAFFERHANS, DEPARTMENT OF BIOCHEMISTRY AT THE TECHNICAL UNIVERSITY OF MUNICH “Just as you can’t see dark matter in the universe using a telescope, you can’t represent dark proteins using conventional methods.” DR PETER WRIGHT, THE SCRIPPS RESEARCH INSTITUTE IN CALIFORNIA
could allow doctors to reach areas that were previously closed off, despite recent medical advancements. On the other hand, researchers have confided to O’donoghue that the discovery of dark matter feels like an admission of failure for medicine – a blank area on a map that was meant to have been fully explored a long time ago.
“We’re amazed at how much we still don’t understand,” admits Schafferhans. From a scientific perspective, the discovery of dark proteins is comparable to “the search for dark matter in the universe,” according to Dr Peter Wright of the Scripps Research Institute in California. Even the world’s most respected scientists feel as if they’ve been thrown back to square one: the search for answers is like groping around a pitch-black room for objects that a human has never seen before.
What O’donoghue and his team have managed to find out about the body’s dark matter shows that, despite its shadowy nature, it plays an important role. The behaviour of dark proteins marks them out as different from regular varieties and contrasts with every known bodily
“Millions of different protein molecules are moving around our bodies – and most of them are ‘dark matter’” BERNHARD KUESTER, PROTEOME RESEARCHER AT THE TECHNICAL UNIVERSITY OF MUNICH
structure. They keep to themselves and hardly ever interact with other proteins, but they still have a far-reaching influence on the body. This independent behaviour would explain why they prefer to float outside cells and glandular tissue.
From examining normal proteins, experts know that these wanderers have highly specialised jobs relating to cellular communication and the immune system. Professor O’donoghue predicts that the discovery of dark proteins will therefore have a widespread impact on the future of medicine. Just like the study of dark matter in physics, dark proteins will usher in a new era of research. And the development has already begun: in China, for instance, scientists -have discovered a link between proteins and the production of antibodies to combat harmful germs. Researchers from the Chinese Academy of Science in Yunnan managed to isolate 700 peptides (short chain proteins) from the dark matter of previously undiscovered proteins. They were so effective at fighting bacteria without side-effects that they could help kickstart a new generation of antibiotics.
But that’s not all. For many researchers, the discovery of dark proteins sheds new light on diseases we still don’t understand. It’s as if a door that was previously locked shut has suddenly opened. Examples include Alzheimer’s and Parkinson’s – both of which are caused by protein aggregation, or clumping. For years, it was clear that a treatment was hiding in the proteome – but it couldn’t be found. Now, after the discovery of dark proteins, a breakthrough is finally within reach.
CAN THE BODY LOSE DNA?
But before we gain complete access to our bodily functions using the dark proteins, there’s another puzzle to solve. Although other research teams have begun mapping the dark matter, more blind spots are appearing in our knowledge of the genome. For example, Professor Akhilesh Pandey, a biochemist at Johns Hopkins University in Baltimore, has identified 193 dark proteins, which, despite being formed from amino acids in the body, don’t have a blueprint in the genome. “The fact that 193 of the proteins came from DNA sequences predicted to be non-coding means that we don’t fully understand how cells read DNA,” explains Professor Pandey. Just as startling is the discovery that 2,000 of the proteins in our bodies might not exist, despite appearing on the gene maps. So what’s the explanation for these phantom proteins? Well, we simply don’t know. The changes that exploring the dark proteins in our body will make to people’s lives is unknown – it could even be as dramatic as the metamorphosis of a caterpillar. But one thing is now certain: whether it’s in the fight against hitherto incurable diseases, boosting life expectancy or tapping into new reserves of power, “dark proteins definitely have an important role,” explains Schafferhans. “But we don’t know what it is yet.”
“Many people think that we’re controlled by our genes. But, in reality, it’s the proteins that do something in us and to us.” PROFESSOR MATTHIAS MANN, PROTEOME RESEARCHER AT THE MAX PLANCK INSTITUTE OF BIOCHEMISTRY