From Genomics to Proteomics: Protein Structure and Public Collaboration
The Human Genome Project (HGP) was a massive scientific undertaking in the field of genomics, the study of genes. At the time of its inception in the early 1990s, many researchers in the field were optimistic that decoding the genome would unlock all the secrets of DNA. However, it has since become clear that the HGP was only the first step toward better understanding DNA and how it may be used to make advances in medicine and biotechnology. In the NOVA special “Cracking the Code of Life,” Professor Eric Lander compares the genome to a parts list: we now have all the parts, in the form of the decoded human genome. The next step is to figure out how all the parts fit together–that is, how a linear genetic sequence translates to a functioning, three dimensional protein.
The HGP and other studies in the field of genomics have provided scientists with the basic tools needed to understand proteins. Now, progress is being made in the cutting-edge field of proteomics, the study of proteins, their shape, and their function. Dr. Craig Venter, founder of Celera Corporation, has stated that “we are the accumulation of our proteins and protein activities.” Indeed, understanding proteins is absolutely essential to unlocking the full potential of DNA. Many researchers believe that further studies in proteomics could yield invaluable insights leading to remarkable improvements in the practical use of DNA in the medical field and elsewhere. However, there are difficulties associated with proteomics that pose a challenge tantamount to (if not greater than) that of genomics and the HGP.
The field of genomics is generally considered less complex than proteomics, and has been an area of study for longer.
Unlike the human genome, which can be translated to and understood as a sequence of letters, proteins cannot be taken out of a three dimensional context. This is because a protein’s structure determines its function. A protein is comprised of amino acid chains. The interactions of the amino acids cause the protein to fold on itself in complex ways, resulting in a unique structure that is suited to the protein’s job. These protein structures be incredibly complex, and furthermore, can be modified in various ways to alter their form and function. In addition, because each protein serves a unique purpose, certain proteins are critical to some cells, while completely unnecessary to others. So, to sum up the difficulties: proteins have complex, variable, three-dimensional structures and not every protein is expressed (produced) in every cell. The field of proteomics may be extremely challenging, but the potential to make invaluable discoveries in the face of adversity has always been a siren song to the scientific community.
What happens, though, when even the top scientific minds in the field are stumped by a problem? The answer could be surprisingly simple: ask the general public for help. As stated above, proteomics can be quite tricky. Finding the exact shape of a protein is difficult when there is a nearly endless number of potential ways for the protein to fold. Public collaboration can be a powerful tool in solving problems that baffle scientists and are too complex to be solved by computer algorithms. Recognizing this, scientists have created a computer game called Foldit that makes it easy for the general public to contribute to scientific discovery. The game is designed for players to help decipher the structures of various proteins. As a starting point, players are given a variety of structures that are known to be incorrect for a certain protein. They can then analyze and alter the structures, tweaking them to improve stability and come closer to the correct structure. While not everyone who plays has a genius level IQ and is able to single-handedly deduce protein structures, every little bit helps. Players can assess and build on work done by others, and fresh perspectives from new members often yield new insights regarding protein structures.
Some might scoff at letting the general public take a swing at seriously complex proteins by way of computer game, but this collaborative effort has already yielded results. Players of Foldit managed to collaboratively discover the structure of a protein responsible for causing a form of AIDS in monkeys and apes. Several key breakthroughs in determining the structure were made via the game, allowing researchers to finally come up with a viable model. From here, scientists hope to develop antiretroviral drugs to fight the virus in monkeys, with an eye towards research to combat HIV in humans.
Perhaps this model of public collaboration will become a central part of scientific research beyond the field of proteomics. Personally, I believe the potential for discovery is incredible, and that collaborative efforts should be pursued in other areas of science. For now, it is certainly a boon to the scientific community, as researchers continue to make inroads in proteomics. For anyone interested in learning more about Foldit, this video explains more about how the game works and what motivates the people who play it.