Through a previous ERC Advanced Grant, Prof. Dek Woolfson’s Protein Design Laboratory at the University of Bristol, UK, developed a new class of synthetic proteins called alpha-helical barrels. Compared with most natural proteins, which are usually solid objects, these are unusual in that they have central accessible barrel-like cavities. Woolfson’s team showed that these cavities take up a blue chemical dye. Moreover, this dye can be displaced by adding other molecules (analytes) to solutions of the barrels with bound dyes, with the new interaction being reported as a loss of the blue colour. Furthermore, through the Advanced Grant, the team had shown that it is possible to generate a wide range of the barrel proteins with cavities of different sizes, shapes and chemistries.
These discoveries led Woolfson’s team to speculate that alpha-helical barrels could form the basis of a new type of sensor system. This was the basis of the ERC Proof of Concept Grant. They proposed to build arrays of different barrel proteins, load them with blue dye, and then challenge the arrays with analytes and complex mixtures. The molecules in these analytes or mixtures would then displace the dyes differentially across the array. This could be imaged to capture a colourimetric fingerprint for the analytes or mixture. In turn, the fingerprints could be analysed by artificial intelligence (in this case, machine learning) to relate the fingerprint to the analyte or mixture. The team call this Barrel Array Diagnostics And SenSing, or BADASS. The idea for the new ERC Proof of Concept Grant was to develop BADASS to see if it could be used in commercial and medical settings.
The new grant employed research scientists to make more barrel proteins, test that they bound to dyes, array them into sensors, and then challenge these with known analytes (e.g. biomarkers for different diseases) and complex test mixtures (e.g. commercial teas) and real-life fluids (e.g. urine, initially from healthy volunteers). The work progressed extremely well on all fronts, and the team has demonstrated that BADASS is robust, that it can detect and predict simple biological molecules ad complex biological mixtures. This work has led to the filing of two patents on the general BADASS platform and on its application to cancer. Moreover, the team have raised £760,000 in business angel funding to spin a new company Rosa Biotech. Rosa is developing the BADASS platform and working with big pharma companies and clinicians to explore its application in biotechnology and medicine.
