Diagnostic Proteins: from Rational Design to Applications in Molecular Medicine and Biology
In-silico-based design of proteins ranging from fluorescent proteins and recombinant antibodies to fusion proteins of interconnected protein modules each having a given function is having an increasing impact in medicine and molecular biology[1.2.3]. Applications of the former include diagnostics and therapeutics, and of the latter, including the measurement of inter and intra-cellular signaling. One innovation whose development was greatly facilitated by CECAM through the E-CAM Centre of excellence combines optically active proteins, sensing domains, and a protein-based molecular switch. Depending on the sensing domains (e.g. antibodies, other suitable proteins, DNA subsequences, etc) - the molecular switch technology has been used, for example, to report via bioluminescence:
- the presence of analytes such as COVID 19 (and other infectious diseases) in diagnostic assays (demonstrated experimentally in assays)
- the upregulation of epidermal growth factor receptor (EGF-R) within living cells (sensing here is done through detection of phosphorylation) which plays an important role in cell growth and transport, and cancer (demonstrated experimentally in living cells)
And there is no reason the same technology cannot be used for problems that are very similar from a rational design and expression perspective, even if from a biological perspective are very different, such as
- NF-kB signaling (via nucleic acid subsequence sensing or alternatively through suitable antibodies), and plays an important role in cancer and inflammation. Indeed a recent report on the creation of synthetic protein phosphorylation circuits that act as logic gates  is intriguing as it suggests an even wider potential scope of application may be possible.
- In the case of Somatic Genomic Testing for metastatic or advanced cancer, the corresponding target nucleic acid sequences or epigenomic aberrations thereof.
- The accurate diagnostic monitoring of such biomarkers, and, in addition, should facilitate the development of novel therapeutic strategies, whose key diagnostic companion is rationally designed from the get-go.
- The rapid improvement of precision of "Point of Care Diagnostic" testing  shows how great the impact of these developments may be for society at large - and not only those fortunate to have easy access to the best medical systems internationally.
Donal MacKernan (University College Dublin) - Organiser
James Sackrison (University College Dublin) - Organiser