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Weldon, M.

Publications and source records attributed to Weldon, M..

3 recordsLinked to original sources

Mixotrophy for carbon-conserving waste upcycling

Modern chemical production, on which human quality of life depends, is unsustainable. Alternative, sustainable manufacturing routes must therefore be developed. Electrochemical and biological processes offer promise for upgrading waste streams, including recalcitrant carbon dioxide and plastic-derived wastes. However, these processes are challenged by the inherent heterogeneity and high energy input requirements for upcycling of the chemical endpoints of the "take-make-waste" economy. Cupriavidus necator is emerging as a potentially useful catalyst to valorize such complex feedstocks because of its extreme metabolic flexibility, which allows it to utilize a wide array of substrates, and its ability to use carbon dioxide directly via the Calvin-Benson-Bassham cycle. C. necator natively oxidizes hydrogen to power carbon utilization, but its inherent flexibility offers an as-yet unexplored opportunity to couple waste stream oxidation with carbon dioxide utilization instead, potentially enabling carbon conservative waste upcycling. Here, we uncover the constraints on carbon conservative chemical transformation using C. necator as a model. We systematically examine the carbon yield and thermodynamic feasibility of mixotrophic scenarios that combine waste-derived carbon sources with hydrogen oxidation to power carbon reassimilation. Then, we evaluate carbon-carbon mixotrophic scenarios, with one carbon source providing electrons in place of hydrogen oxidation. We show that both hydrogen and ethylene glycol have high potential as electron sources to drive carbon-neutral or carbon-negative mixotrophic upgrading of waste streams such as acetate or butyrate. In contrast, we find that carbon conservation is likely infeasible for most other waste-derived carbon sources. This work provides a roadmap to establishing novel C. necator strains capable of carbon efficient waste upcycling.

bioengineering↗

Discovery of neuronal cell types by pairing whole cell reconstructions with RNA expression profiles

Effective classification of neuronal cell types requires both molecular and morphological descriptors to be collected in situ at single-cell resolution. However, current spatial transcriptomics techniques are not compatible with imaging workflows that successfully reconstruct the morphology of complete axonal projections. Here, we introduce a new method, which we call morphoFISH, that combines tissue clearing, submicron whole-brain two photon imaging, and Expansion-Assisted Iterative Fluorescence In Situ Hybridization (EASI-FISH) to assign molecular identities to fully reconstructed neurons in the mouse brain. We used morphoFISH to molecularly identify a previously unknown population of cingulate neurons projecting ipsilaterally to the dorsal striatum and contralaterally to higher-order thalamus. By pairing whole-brain morphometry, improved techniques for nucleic acid preservation and spatial gene expression, morphoFISH offers a quantitative solution for discovery of multimodal cell types and complements existing techniques for characterization of increasingly fine-grained cellular heterogeneity in brain circuits.

neuroscience↗

Reconstruction of 1,000 projection neurons reveals new cell types and organization of long-range connectivity in the mouse brain

Neuronal cell types are the nodes of neural circuits that determine the flow of information within the brain. Neuronal morphology, especially the shape of the axonal arbor, provides an essential descriptor of cell type and reveals how individual neurons route their output across the brain. Despite the importance of morphology, few projection neurons in the mouse brain have been reconstructed in their entirety. Here we present a robust and efficient platform for imaging and reconstructing complete neuronal morphologies, including axonal arbors that span substantial portions of the brain. We used this platform to reconstruct more than 1,000 projection neurons in the motor cortex, thalamus, subiculum, and hypothalamus. Together, the reconstructed neurons comprise more than 75 meters of axonal length and are available in a searchable online database. Axonal shapes revealed previously unknown subtypes of projection neurons and suggest organizational principles of long-range connectivity.

neuroscience↗