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European Biopharmaceutical Review

Details Matter

The transition from uni- to multicellular organisms was marked by an increase in the complexity of cell surface proteins that allowed intercellular communication and stable cell adhesion (1). The surfaceome (the collection of proteins residing at the cell surface) acts as the interface between a cell and its environment, mediating crucial cellular behaviours such as cell-cell communication, self and non-self recognition, and cell signalling. Additionally, the surfaceome largely dictates the shape, polarity, differentiation, and motility of cells. Given the crucial role of surface-associated proteins in every aspect of cellular life, they are, unsurprisingly, the molecular targets for roughly 70% of FDA approved drugs (2).

The aforementioned functions of the surfaceome are mediated through interactions of proteins in the cell membrane of the same cell (cis) and through interactions with proteins of neighbouring cells, the extracellular matrix, and circulating ligands (trans). The collection of cis and trans interactions is overall referred to as extracellular proteinprotein interactions (ePPIs). For a cell to adapt quickly in a changing microenvironment and respond fast to stimuli while retaining the necessary plasticity, ePPIs are usually transient with low affinities (μM to mM range) to allow for fast dissociation rates. Additionally, surface proteins have a few distinct properties compared to their intracellular counterparts. Firstly, correct folding of these proteins is largely dependent on an oxidising environment for the formation of disulphide bonds. Secondly, given that more than 90% of vertebrate surface proteins are glycosylated, correct folding also requires specialised chaperons and glycosylation machinery (3). Thirdly, membrane-spanning proteins are largely amphipathic due to hydrophilic glycans decorating the extracellular part and stretches of hydrophobic amino acids that span the membrane.

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Dr Maria P Pavlou received her PhD in translational proteomics from the Department of Laboratory Medicine and Pathobiology at University of Toronto, Canada. Upon PhD completion, Maria moved to Switzerland to pursue a postdoctoral fellowship in the Institute of Molecular Systems Biology at the Swiss Federal Institute of Technology (ETH) in Zürich, focussing on host-pathogen interactions. In 2017, she joined Dualsystems Biotech as a senior scientist, and, a year later, she was promoted to Chief Scientific Officer, leading the research team to develop further the LRC methodology and establish new services.

Dr Paul Helbling did his Master’s degree in biology at the University of Zürich, Switzerland, and obtained his PhD in developmental biology at ETH Zürich. After his PhD, he worked at the Foundation for Cardiovascular Research and organised clinical studies according to Good Clinical Practice. Paul then moved on to MDS Pharma Services, where he became responsible for the ligand binding group that specialised inthe analysis of biologics and antidrug antibodies. His next position was in business development at Solvias, responsible for southern Europe and Germany and opening new market territories in Turkey. Paul then became Head of Business Development at IBR, before joining the team at Dualsystems Biotech as CEO, focussing on identifying targets and off-targets on the living cells using liquid chromatographymass spectrometry.
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Dr Maria P Pavlou
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Dr Paul Helbling
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