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European Biopharmaceutical Review

Becoming Better Informed

Increasing success rates and speed to failure requires more information. We need to know which proteins to target, which molecules to use and to which patients drugs should be administered. The devil, as always, is in the details. Cell-based screening, computational modelling and ribosomal profiling, among other recent improvements, are informative – but do not seem to be the solution. Clearly, another approach is needed. Mine is premised on three assumptions:

  1. Proteomics represents the most abundant and useful pool of biological information
  2. Post-translational modification (PTM) is the defining feature of human proteins
  3. Mass spectrometry (MS) is a structurally flawed tool for accessing these data

Proteomics is King

Blueprints and recipes contain assembly instructions; genomes do not. Our approximately 20,000 human genes get spliced into about 100,000 unique transcripts variable across development and cell type (1). TP53, one of the best-studied proteins in humans, has at least 15 structurally and functionally distinct isoforms (2). In point of fact, the previous statement betrays a biological error shared by MS – namely that TP53 is a gene, not a protein. Ignoring splice variation makes conversation simpler, but masks the molecular complexity we require to exist and survive.

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Christian Loch is co-founder and Director of R&D at AVMBioMed. He is also adjunct faculty in the Department of Chemistry at Villanova University, US, where he teaches proteomics in the graduate school. Christian has 10 years of industry experience and holds an MPH in Epidemiology from the University of Washington, US, and a PhD in Biochemistry from the University of Virginia, US.
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Christian Loch
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