Image credit: MRC Laboratory of Molecular Biology
Scientists develop technique to control proteins inside cells with potential to treat disease
2 Nov 2017
In 2015, scientists at the MRC Laboratory of Molecular Biology (LMB) developed a new technique using ‘designer molecules’ to control proteins inside living cells. Named BOLT, this technique could allow scientists to control defective proteins involved in many diseases.
Proteins are the major component of cells in all living species, from the tiniest microbes to the largest mammals. All proteins are the products of complex cellular machinery, which assemble building blocks, known as amino acids, according to a genetic blueprint. This assembly takes place within the cell inside ‘protein factories’ known as ribosomes. The genetic blueprint is translated using a dictionary – or genetic code – that is common to all living species.
The genetic code is extraordinarily elegant, but in nature it has a limited vocabulary. It is able to inform the construction of just 20 different amino acids. Dr Jason Chin at the MRC LMB has challenged this fundamental principle in molecular biology by reprogramming the genetic code to produce ‘unnatural amino acids’, vastly expanding the vocabulary of life. By re-engineering ribosomes to produce these unnatural amino acids, Dr Chin and his team are building a parallel biological system that will have a vast array of potential applications.
One such application is BOLT -- bio-orthogonal ligand tethering -- a technique developed by Dr Chin in 2015. BOLT addresses a common problem encountered when trying to target defective proteins with inhibitor drugs. Defective proteins are involved in several diseases including cancer, so they are an attractive target for drug development. Many proteins belong to families, where the related proteins are very similar in sequence and structure, but have slightly different roles within the cell. Selectively targeting an individual protein with a drug can often be impossible because the drug binding site on the protein is identical in all the family members. As a result, several proteins would be affected by a single drug, and unfortunately even the most promising drug can end up being too unspecific to be useful. The lack of specificity is a problem as it can cause unwanted side effects. However, using the insights gained from reprogramming the genetic code, Dr Chin has genetically engineered an entirely new site into the target protein, which could help solve this problem.
Dr Chin and his team have found an innovative solution to a common problem in drug design. The technology behind reprogramming the genetic code to create unnatural amino acids has resulted in the filing and licensing of many patent applications, along with early discussions into founding a spin-out company to commercialise these designer protein molecules. By challenging one of the central principles of molecular biology, Dr Chin has enhanced our understanding of one of the most important processes of life. The applications of this technology could revolutionise the way we treat disease and improve human health.
Award details: MC_U105181009