Biology subjects

Black, H.

Publications and source records attributed to Black, H..

4 recordsLinked to original sources

bioRxiv2026

When clades collide: Genomic admixture in blacklegged ticks (Ixodes scapularis) from the Great Plains

Ixodes scapularis ticks transmit a number of pathogens important to human health, including Borrelia burgdorferi, the causative agent of Lyme disease. While I. scapularis is found across the Eastern United States, Lyme disease transmission is largely limited to the Northeast and Upper Midwest and is nearly absent in the South. This indicates that differences in northern versus southern clades of I. scapularis are associated with differences in Lyme disease transmission risk. I. scapularis is undergoing range expansion, including into the Great Plains region of the United States. Determining where I. scapularis populations in the Great Plains originated can inform future risk of Lyme disease transmission in this region. In this study, we use a population genomics framework to characterize diversity, structure, and B. burgdorferi infection rates of I. scapularis populations in the Great Plains region. We generated whole genome sequence data and single nucleotide polymorphism (SNP) datasets from I. scapularis ticks collected in Iowa, Kansas, Nebraska, and South Dakota to compare to publicly available data from across the species range. Our analysis of 200 I. scapularis SNP datasets indicated geographically well-defined populations that correspond to historical northern and southern ancestral clades of I. scapularis. Ticks from South Dakota, Iowa, and northeastern Nebraska are genetically similar populations from the Upper Midwest, while ticks from Kansas are more genetically similar to ticks from the Southeast. Ticks collected in the central eastern region of Nebraska, however, represent an evenly admixed population of both northern and southern genomic backgrounds. Analysis of B. burgdorferi reads from genomic datasets shows [~]50% infection rate in ticks from Iowa and northeastern Nebraska, whereas ticks from Kansas show no evidence of B. burgdorferi infection. Of note, evenly admixed ticks from the central eastern region of Nebraska also show no evidence of B. burgdorferi infection. These results provide further evidence that tick genomics may influence traits associated with B. burgdorferi infection status, and thus the potential for Lyme disease transmission. As the range of I. scapularis continues to expand, bringing historically isolated populations into contact, there is a clear need to understand the consequence of genomic admixture for B. burgdorferi transmission potential to inform future risk of Lyme disease in the United States.

genomics↗

bioRxiv2025

Ataxin-2 knockdown is neuroprotective via cell-autonomous and non-cell-autonomous mechanisms

Ataxin-2 (ATXN2) is a genetic modifier of TDP-43 toxicity and a promising therapeutic target in amyotrophic lateral sclerosis (ALS). However, the mechanisms underlying its neuroprotective effects remain poorly understood. Here we show that ataxin-2 reduction confers neuroprotection by engaging adaptive metabolic programs in both neuronal and glial cells. Using global proteomic profiling in yeast and mouse TDP-43 models, we establish that pbp1/ataxin-2 (pbp1 is the yeast ataxin-2 ortholog) activates orthogonal stress-adaptive programs that enable alternative energy production and augment trophic support, rather than simply reversing TDP-43-induced damage. In neurons, ataxin-2 downregulation activates glycolysis and reductive glutamine carboxylation driven by IDH1, restoring ATP production independently of impaired mitochondria. In astrocytes, ataxin-2 downregulation upregulates cholesterol biosynthesis via HMGCS1, enhancing trophic support to neurons in a non-cell-autonomous manner. Full neuroprotection requires both mechanisms: neuronal survival is only completely rescued when ataxin-2 is reduced in the context of neuron-astrocyte co-cultures. Importantly, ataxin-2 downregulation protects against both TDP-43 gain-of-function and loss-of-function toxicity, broadening its therapeutic relevance. Collectively, our findings reveal novel mechanisms by which ataxin-2 orchestrates adaptive metabolic resilience and establish ataxin-2 as a regulator of stress-adaptive response in brain cells under the conditions of stress.

neuroscience↗

bioRxiv2023

Development of covalent chemogenetic K2P channel activators

K2P potassium channels regulate excitability by affecting cellular resting membrane potential in the brain, cardiovascular system, immune cells, and sensory organs. Despite their important roles in anesthesia, arrhythmia, pain, hypertension, sleep, and migraine, the ability to control K2P function remains limited. Here, we describe a chemogenetic strategy termed CATKLAMP (Covalent Activation of TREK family K+ channels to cLAmp Membrane Potential) that leverages the discovery of a site in the K2P modulator pocket that reacts with electrophile-bearing derivatives of a TREK subfamily small molecule activator, ML335, to activate the channel irreversibly. We show that the CATKLAMP strategy can be used to probe fundamental aspects of K2P function, as a switch to silence neuronal firing, and is applicable to all TREK subfamily members. Together, our findings exemplify a new means to alter K2P channel activity that should facilitate studies both molecular and systems level studies of K2P function and enable the search for new K2P modulators.

biophysics↗

bioRxiv2023

The gag-like gene RTL8 antagonizes PEG10-mediated virus like particles in humans

PEG10 is a retroelement-derived Mart-family gene that is necessary for placentation and has been implicated in neurological disease. PEG10 resembles both retrotransposon and retroviral proteins and forms virus-like particles (VLPs) that can be purified using iodixanol ultracentrifugation. It is hypothesized that formation of VLPs is crucial to the biological roles of PEG10 in reproduction and neurological health. Here, we describe the regulation of PEG10 VLP formation and release in human cells with a role for the related Mart gene RTL8. RTL8 resembles a truncated form of PEG10 that shares homology with the N-terminal gag-like capsid domain. Alone, RTL8 is unable to form VLPs, but was incorporated into PEG10-derived particles. RTL8 co-expression decreased the abundance of PEG10 VLPs and increased intracellular levels of PEG10, suggesting a model where RTL8 inhibits PEG10 VLP formation or release. Consistent with this model, RTL8 bound to the N-terminal domain of PEG10 capsid, and modulation of RTL8 influenced PEG10-derived VLP abundance in naturally producing cells. RTL8 is broadly expressed in many of the same tissues as PEG10, including in human brain. Taken together, these results describe a novel antagonistic relationship between two human retroelement-derived genes and have implications for our understanding of PEG10 biology and disease.

cell biology↗