A multinational team of scientists, comprising 7 research groups from 3 different countries, had sifted through the cells of 9 different species representing the entire tree of life, which led them to discovering a great number of previously-unknown interactions between individual proteins within a cell.
This tour-de-force of protein science, led by Professor Andrew Emili from the University of Toronto‘s Donnelly Centre and Professor Edward Marcotte from the University of Texas, Austin, was published on September 7 in the science journal Nature.
The sequencing of the human genome over a decade ago, although a remarkable achievement in the field of biology, has only scratched the surface of our understanding of how cells operate. While genes provide a blueprint for the interior workings of an organism, the “work” itself is carried out by proteins – and there are tens of thousands of them in human cells – by sticking together to form what are called “molecular machines” that build new proteins, recycle old ones and perform many other crucial functions.
To further our knowledge of these cellular mechanisms – most of which are still obscure to science – Emili and Marcotte’s team used state-of-the-art equipment and research methodologies to fish out thousands of discrete protein interactions and then plugged them into a network that offers clues into their function based on which other proteins they bind with.
The new map expands the number of known protein associations over 10 fold, and gives insights into how they evolved over time.
“For me the highlight of the study is its sheer scale. We have tripled the number of protein interactions for every species. So across all the animals, we can now predict, with high confidence, more than 1 million protein interactions – a fundamentally “big step” moving the goal posts forward in terms of protein interactions networks,” said Emili.
Fascinatingly, the research team has found that tens of thousands of protein associations have reached us unchanged from the very first ancestral cell, which appeared on Earth around a billion years ago. According to Marcotte, the fact that these assemblies are also found in humans not only reinforces what we already know about our common evolutionary past, but also provides the opportunity to study the genetic basis of disease and how it presents in different species.
Proving this is more than just empty rhetoric, the team has shown that various abnormalities in one of the molecular machines they’d uncovered in their research, dubbed Commander, may play a key role in the onset of a number of intellectual disabilities in humans. Genes that code for some of Commander’s component parts had been previously implicated in several brain disorders, which the researchers confirmed by showing that a disruption of the normal functioning of this clump of proteins in tadpoles causes a distinct misalignment of neurons in a developing embryo.
“With tens of thousands of other new protein interactions, our map promises to open many more lines of research into links between proteins and disease, which we are keen to explore in depth over the coming years,” concludes Professor Emili.