overlake.bio is an end-to-end decentralized science (DeSci) framework comprising a collection of projects aimed at promoting human longevity.<br>
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The framework comprises four projects:<br>
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1| Enzyme engineering for crosslinked collagen turnover<br>
To design matrix metalloproteinases for extracellular matrix rejuvenation.<br>
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2| Extracellular matrix aging atlas<br>
To assemble a knowledgebase of time-resolved matrisome signatures extracted from public proteomic datasets.<br>
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3| Advanced glycation end product (AGE)-degrading enzymes<br>
To engineer biologics to alleviate the glycation load.<br>
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4| Glycation of ribosomes as a driver of proteostasis loss<br>
To produce novel insights into translation fidelity in aging. [preprint]
De-/reconstructing the ground substance.
While most efforts in the longevity biotechnology industry are directed toward intracellular processes, overlake.bio explores the cellular environment, represented by the extracellular matrix (ECM). Operating at the intersection of molecular biology, mechanobiology, and biochemistry, the project offers a comprehensive framework for targeting hitherto irreparable forms of age-related damage.
De novo engineering of enzymes with enhanced functionalities and/or custom target specificities opens broad possibilities for achieving cellular resilience, damage repair, and carrying out novel reactions, working towards optimal human health and longevity. The project aims to ameliorate the mechanosensory burden of the aged ECM through computational biology and reaction-conditioned enzyme engineering to promote youthful ECM remodeling. With its scope outside the cell-centric view on aging, the project addresses a critical conceptual and technological gap within modern longevity research, aiming to extend the healthy human lifespan by leveraging the body’s intrinsic ability to restore itself, engineering the ECM turnover.
