Biology subjects

Morse, R.

Publications and source records attributed to Morse, R..

3 recordsLinked to original sources

bioRxiv2025

COVID-19 vaccination induces cross-neutralisation of sarbecoviruses related to SARS-CoV-2

Close relatives of SARS-CoV-1 and SARS-CoV-2 continue to circulate in wildlife, posing an ongoing threat of zoonotic spillover. While vaccination played a key role in controlling the COVID-19 pandemic, variants of concern (VOC) with immune evasive substitutions emerged on multiple occasions, causing widespread breakthrough infections. The combined threats of zoonosis and newly emerging VOCs, coupled with the potential for recombination, underscore the need to assess the breadth of existing vaccine-mediated protection. Here, we investigate a cohort of older individuals (median age 68.5 years) for the potential of cross-neutralisation against Omicron lineage VOC and animal sarbecoviruses induced by four COVID-19 vaccine doses. Despite the recent use of a bivalent mRNA vaccine dose (encoding spike from Wu-1 and omicron), we observed that neutralisation of Omicron lineage VOCs such as BA.1 and BA.2 were reduced compared to SARS-CoV-2 Wu-1, suggesting an imprinted immune response from pre-Omicron lineage viruses. Similarly, both SARS-CoV-1 and a SARS-CoV-1-related bat CoV were neutralised less efficiently than SARS-CoV-2 Wu-1. Unexpectedly, however, we observed that two animal SARS-CoV-2-related viruses, BANAL-20-52 (from bats) and a pangolin-CoV, were more sensitive to serum neutralising antibodies than SARS-CoV-2 Wu-1 itself. These surprising findings suggest that vaccine-mediated adaptive immunity may provide efficient cross-protection against certain animal sarbecoviruses.

microbiology↗

bioRxiv2022

Contrast-polarity specific mapping optimizes neuronal computation for collision detection

Neurons receive information through their synaptic inputs, but the functional significance of how those inputs are mapped on to a cells dendrites remains unclear. We studied this question in a grasshopper visual neuron that tracks approaching objects and triggers escape behavior before an impending collision. In response to black approaching objects, the neuron receives OFF excitatory inputs that form a retinotopic map of the visual field onto compartmentalized, distal dendrites. Subsequent processing of these OFF inputs by active membrane conductances allows the neuron to discriminate the spatial coherence of such stimuli. In contrast, we show that ON excitatory synaptic inputs activated by white approaching objects map in a random manner onto a more proximal dendritic field of the same neuron. This random synaptic arrangement results in the neurons inability to discriminate the coherence of white approaching stimuli. Yet, the neuron retains the ability to discriminate stimulus coherence for checkered stimuli of mixed ON/OFF polarity. The coarser mapping and processing of ON stimuli thus has a minimal impact, while reducing the total energetic cost of the circuit. Further, we show that these differences in ON/OFF neuronal processing are behaviorally relevant, being tightly correlated with the animals escape behavior to light and dark stimuli of variable coherence. Our results show that the synaptic mapping of excitatory inputs affects the fine stimulus discrimination ability of single neurons and document the resulting functional impact on behavior.

neuroscience↗

bioRxiv2019

Kin28 depletion increases association of TFIID subunits Taf1 and Taf4 with promoters in Saccharomyces cerevisiae

In eukaryotes, transcription of mRNA-encoding genes by RNA polymerase II (Pol II) begins with assembly of the pre-initiation complex (PIC), comprising Pol II and the general transcription factors. Although the pathway of PIC assembly is well established, the mechanism of assembly and the dynamics of PIC components are not fully understood. For example, only recently has it been shown in yeast that the Mediator complex, which assists in pre-initiation complex formation at promoters of essentially all genes transcribed by Pol II, normally occupies promoters only transiently. This was inferred from studies showing that inhibiting Pol II promoter escape by depleting or inactivating Kin28 resulted in increased promoter occupancy by Mediator, as measured by chromatin immunoprecipitation (ChIP). Here we show that two subunits of TFIID, Taf1 and Taf4, similarly show increased occupancy as measured by ChIP upon depletion or inactivation of Kin28. In contrast, TBP occupancy is unaffected by depletion of Kin28, thus revealing an uncoupling of Taf and TBP occupancy during the transcription cycle. Increased Taf1 occupancy upon Kin28 depletion is suppressed by depletion of TBP, while depletion of TBP in the presence of Kin28 has little effect on Taf1 occupancy. Taf1 occupancy relative to TBP is higher at TFIID-dominated promoters and promoters having consensus TATA elements than at SAGA-dominated promoters and promoters lacking consensus TATA elements, consistent with prior work, and the increase in Taf occupancy upon depletion of Kin28 is more pronounced at TFIID-dominated promoters. Our results support the suggestion, based on recent structural studies, that TFIID may not remain bound to gene promoters through the transcription initiation cycle.\n\nAuthor SummaryTranscription of mRNA-encoding genes by RNA polymerase II (Pol II) begins when the pre-initiation complex, a large complex comprising Pol II and several general transcription factors, including the TATA-binding protein (TBP)-containing TFIID complex, assembles at gene promoters. Although the major steps in the pathway of PIC assembly have been identified, the mechanism of assembly in vivo and the dynamics of PIC components are not fully understood. In this work we have used a yeast strain that is engineered to allow inhibition of promoter escape by Pol II by administration of a chemical, in order to \"freeze\" the assembled PIC and thus determine whether this condition increases the promoter occupancy of TBP and two TBP-associated factors (Tafs) that are components of TFIID. This approach was used recently to demonstrate that the Mediator complex, which facilitates PIC assembly, normally binds only transiently to gene promoters. We find that Tafs, like Mediator, show increased occupancy when Pol II promoter escape is inhibited, whereas TBP binding is constant. These results imply that binding of TBP and Tafs is uncoupled during the transcription cycle, and that Taf occupancy is at least partially interrupted upon Pol II promoter escape.

genetics↗