Abstract
Antibodies (Abs) have a proven track record in biotechnology and biomedical sciences. Many applications (both academic research and industry) are based on conventional Abs (mostly IgGs). However, despite their track record, conventional Abs have their drawbacks. These shortcomings can usually be overcome by unconventional Abs found in other mammals. A prime example is provided by the Belgian discovery of a peculiar Ab subset that naturally occurs in camelids (e.g., camels, dromedaries, and llamas). In these Abs, antigen recognition is mediated by a single domain, which is why this domain is referred to as a "single-domain antibody" (sdAb aka nanobody®). Camelid sdAbs possess unique features that are not usually found in conventional Abs: a small size (~15 kDa), an increased solubility, robust folding properties, a high intrinsic stability, poor immunogenicity, and the relative ease to tailor them (modifications according to a "plug-and-play" principle). These remarkable properties render them highly suitable for fundamental and translational research in life sciences.
The Laboratory of Medical Biochemistry (LMB) has spearheaded the establishment of an in-house camelid sdAb platform through which it is possible to obtain sdAbs through camelid immunisation and/or in silico designed synthetic libraries. In the past years, we have immunized four llamas with recombinant versions of proteins that play an important role in human pathophysiology. These target antigens represent the core foci of the research lines of the two PIs at LMB: i) human proteases involved in inflammation and immunity (Ingrid De Meester) and ii) surface antigens operating at the interface between protozoan parasites and their vertebrate hosts (Yann Sterckx). More specifically, we have immunised with >15 targets thereby yielding >50 unique sdAbs, which now need to be investigated in-depth. This initiative is part of the overall, long-term vision for LMB. The lab's activities are steadily being organized into three pillars that will underpin current and future initiatives: i) use of biochemistry, biophysics, structural biology, and functional assays to unravel the structure-function relationship of proteins involved in human pathophysiology, ii) establishment of a "hybrid" sdAb generation and engineering platform, and iii) the use of sdAbs as research and discovery tools to address fundamental questions. We therefore strategically choose to employ this seed funding to appoint a post-doctoral researcher with a high level of expertise and experience in the generation, identification and application of camelid sdAbs. In turn, this will contribute to the consolidation of sdAb-driven research at LMB (and thus the University of Antwerp).
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