Proteomics in a systems biology framework
Proteomics in a systems biology framework is the primary molecular research approach elevating our ecological and One Health activities. Understanding how a bodily system works requires knowing more than which genes are expressed in each cell: it is crucial to know in what form cellular proteins are expressed, whether they are active or not, and with what other molecules the immune pathway proteins interact, which can only be measured by proteomics. Integration of various ΓÇÿomics' and other phenotypic data to predict specific, testable responses comprises systems biology. We apply systems biology to One Health studies to discover critical differences between the proteins expressed in infected animal vs. human cells, especially host proteins that are cut by viral proteases to enable replication and evasion of innate immunity defences. Leveraging our expertise in proteases, proteomics, degradomics, informatics, structural biology, and drug development, we are identifying viral substrates crucial for immune and vaccine escape and drug resistance of SARS-CoV-2 and disease-causing variants in animal and human cells. We are zeroing in on our novel therapeutic development activities on (a) common vs. unique proteins that promote infection, e.g., proteases, that can be blocked by inhibitor drugs, (b) host cell antiviral protective proteins that can be elevated in amounts by mRNA therapy to increase their effective levels of protection, and (c) host protein substrates that are cut in infection that we will restore to combat the virus using a new class of antivirals, termed ΓÇ£molecular correctorsΓÇ¥, as a swath of new antiviral therapies. By understanding fundamental host defence system pathways and their interconnections, our findings will be broadly applicable to multiple viral infectious diseases and those with inflammatory complications, particularly in immunocompromised, unvaccinated, or marginalized populations. Thus, we are preparing for the next outbreak or pandemic using a logical and holistic approach to the problem of pandemics.
