Biology subjects

McClelland, A.

Publications and source records attributed to McClelland, A..

3 recordsLinked to original sources

bioRxiv2026

Compositional Heterogeneity Structures Microbial Microhabitats across Distinct Mineral Substrates

Microbial communities living on and in rocks operate at the microscale, where interactions with minerals fundamentally shape community structure and function. Yet the relationship between micron scale mineralogical configurations and microbial distributions remains poorly understood. We tested the hypothesis that microbial biomass spatially correlates with areas of heightened mineralogical heterogeneity by applying Raman microspectroscopy to rock samples from three geologically distinct substrates: authigenic carbonates from a marine methane seep, volcanic basalt from Iceland, and polymetallic nodules from the abyssal seafloor. Using spectral decomposition and multiple complementary metrics of compositional heterogeneity, we evaluated intra-pixel and inter-pixel heterogeneity patterns in relation to biomass distribution. Our analyses reveal three patterns across all sample types. 1) When spectra are deconstructed into their constituent components, biomass zones are disproportionately dominated by the biomass spectral component compared with primary mineral components in zones of different minerals. 2) Biomass spectra have more homogeneous compositional profiles than mineral spectra. 3) Biomass is surrounded by more heterogeneous microhabitats than mineral pixels. These findings demonstrate that biomass exerts a distinctive and consistent influence on Raman spectral signatures, both within and between pixels, in ways that mineral components do not. Our results establish generalizable principles linking microscale mineralogical properties to microbial biogeography; these properties could be used as a potential biosignature and may provide a standardized workflow applicable to diverse rock systems and astrobiological exploration strategies.

microbiology↗

bioRxiv2021

The NK receptor NKp46 recognizes ecto-calreticulin on ER-stressed cells

Natural killer cells (NK) are a first line of immune defense to eliminate infected, transformed and stressed cells by releasing cytotoxic granules1. NK activation is controlled by the balance of signals transmitted by activating and inhibitory receptors but activating receptor engagement is required to trigger cytotoxicity. The activating receptor NKp46, encoded by the NCR1 gene, is expressed by virtually all NK cells and is the most evolutionarily ancient NK receptor. NKp46 plays a major role in NK recognition of cancer cells, since NKp46 blocking antibodies potently inhibit NK killing of many cancer targets2,3. Although a few viral, fungal and soluble host ligands4 have been identified, the endogenous cell-surface ligand of this important activating NK receptor is unknown. Here we show that NKp46 recognizes and is activated by the P-domain of externalized calreticulin (ecto-CRT). CRT, normally localized to the ER, translocates to the cell surface during ER stress and is a hallmark of chemotherapy-treated dying cancer cells that induce an immune response (immunogenic cell death, ICD)5. NKp46 caps with ecto-CRT in NK immune synapses formed with ecto-CRT-bearing target cells. ER stress, induced by ZIKV infection, ICD-causing chemotherapy drugs and some senescence activators, externalizes CRT and triggers NKp46 signaling. NKp46-mediated killing is inhibited by CRT knockout or knockdown or anti-CRT antibodies and is enhanced by ectopic expression of GPI-anchored CRT. NCR1/Ncr1-deficient human and mouse NK are impaired in killing ZIKV-infected, ER-stressed, and senescent cells and cancer cells that endogenously or ectopically express ecto-CRT. Importantly, NKp46 recognition of ecto-CRT controls the growth of B16 melanoma and RAS-driven lung cancer in mouse models and enhances tumor-infiltrating NK degranulation and cytokine secretion. Thus, ecto-CRT is a danger-associated molecular pattern (DAMP) that is an endogenous NKp46 ligand that promotes innate immune elimination of ER-stressed cells.

immunology↗

bioRxiv2020

A native chemical chaperone in the human eye lens

Cataract is one of the most prevalent protein aggregation disorders and still the most common cause of vision loss worldwide. The metabolically quiescent core region of the human lens lacks cellular or protein turnover; it has therefore evolved remarkable mechanisms to resist light-scattering protein aggregation for a lifetime. We now report that one such mechanism involves an unusually abundant lens metabolite, myo-inositol, suppressing aggregation of lens crystallins. We quantified aggregation suppression using our previously well-characterized in vitro aggregation assays of oxidation-mimicking human {gamma}D-crystallin variants and investigated myo-inositols molecular mechanism of action using solution NMR, negative-stain TEM, differential scanning fluorometry, thermal scanning Raman spectroscopy, turbidimetry in redox buffers, and free thiol quantitation. Unlike many known chemical chaperones, myo-inositols primary target was neither the native nor the unfolded state of the protein, nor the final aggregated state, but rather the rate-limiting bimolecular step on the aggregation pathway. Given recent metabolomic evidence that it is severely depleted in human cataractous lenses compared to age-matched controls, we suggest that maintaining or restoring healthy levels of myo-inositol in the lens may be a simple, safe, and globally accessible strategy to prevent or delay lens opacification due to age-onset cataract.

biophysics↗