Biology subjects

Hennigan, S.

Publications and source records attributed to Hennigan, S..

4 recordsLinked to original sources

bioRxiv2025

Characterisation of spinal ligaments in the embryonic chick

Ligaments are important connective tissues within the musculoskeletal system that connect bone to bone and provide support and stability. The spine contains a number of ligaments that predominantly function in mechanical stabilisation and allow for certain ranges of spinal motion. Establishment of mechanical stability provided by spinal ligaments has not been described, and it is not known to what extent failure or inadequate spinal ligaments contribute to spinal conditions, such as scoliosis. While there are many similarities between ligaments and tendons, there is no experimental evidence investigating the development of these stability bearing tissues. This study uses the embryonic chick model Gallus gallus and investigates the development of spinal ligaments in the thoracic spine, examining structure and molecular expression across development. Findings show organisational changes in spinal ligaments in association with vertebral shape changes from cranial to caudal, with the anatomical identification of six vertebral ligaments in the thoracic spine. As development proceeds the size of the anterior longitudinal ligament, on the ventral surface of the vertebral body, and the supraspinous ligament, on the dorsal side of the spine, becomes greater, with the orientation of collagen fibres in the supraspinous ligament becoming more aligned. In addition, this study demonstrates that cell density decreases and nuclei become smaller and more circular across development. This study provides evidence that the embryonic chick is an appropriate model to study spinal ligament development and has added knowledge on the structural hallmarks of embryonic vertebral ligament tissues. These findings allow for subsequent investigation of the mechanical and molecular characteristics of spinal ligament development, for example useful for determining if in utero movement is important for the establishment of spinal ligament stability. Use of this model and integration of findings with additional models will provide knowledge of the contribution of spinal ligaments in spinal failure conditions.

developmental biology↗

bioRxiv2018

Co-circulating mumps lineages at multiple geographic scales

Despite widespread vaccination, eleven thousand mumps cases were reported in the United States (US) in 2016-17, including hundreds in Massachusetts, primarily in college settings. We generated 203 whole genome mumps virus (MuV) sequences from Massachusetts and 15 other states to understand the dynamics of mumps spread locally and nationally, as well as to search for variants potentially related to vaccination. We observed multiple MuV lineages circulating within Massachusetts during 2016-17, evidence for multiple introductions of the virus to the state, and extensive geographic movement of MuV within the US on short time scales. We found no evidence that variants arising during this outbreak contributed to vaccine escape. Combining epidemiological and genomic data, we observed multiple co-circulating clades within individual universities as well as spillover into the local community. Detailed data from one well-sampled university allowed us to estimate an effective reproductive number within that university significantly greater than one. We also used publicly available small hydrophobic (SH) gene sequences to estimate migration between world regions and to place this outbreak in a global context, but demonstrate that these short sequences, historically used for MuV genotyping, are inadequate for tracing detailed transmission. Our findings suggest continuous, often undetected, circulation of mumps both locally and nationally, and highlight the value of combining genomic and epidemiological data to track viral disease transmission at high resolution.

genomics↗

bioRxiv2018

Capturing diverse microbial sequence with comprehensive and scalable probe design

Metagenomic sequencing has the potential to transform microbial detection and characteri zation, but new tools are needed to improve its sensitivity. We developed CATCH (Compact Aggregation of Targets for Comprehensive Hybridization), a computational method to enhance nucleic acid capture for enrichment of diverse microbial taxa. CATCH designs compact probe sets that achieve full coverage of known sequence diversity and that scale well with this diversity. To illustrate applications of CATCH, we focused on capturing viral genomes. We designed, synthesized, and validated multiple probe sets, including one that targets whole genomes of the 356 viral species known to infect humans. Capture with these probe sets enriched unique viral content on average 18x and allowed us to assemble genomes that we could not otherwise recover, while accurately preserving within-sample diversity. We used this approach to recover genomes from the 2018 Lassa fever outbreak in Nigeria and to improve detection of viral infections in samples with unknown content. Together, this work demonstrates a path toward more sensitive, cost-effective metagenomic sequencing.

genomics↗

bioRxiv2017

Genome sequencing reveals Zika virus diversity and spread in the Americas

Despite great attention given to the recent Zika virus (ZIKV) epidemic in the Americas, much remains unknown about its epidemiology and evolution, in part due to a lack of genomic data. We applied multiple sequencing approaches to generate 110 ZIKV genomes from clinical and mosquito samples from 10 countries and territories, greatly expanding the observed viral genetic diversity from this outbreak. We analyzed the timing and patterns of introductions into distinct geographic regions; our phylogenetic evidence suggests rapid expansion of the outbreak in Brazil and multiple introductions of outbreak strains into Puerto Rico, Honduras, Colombia, other Caribbean islands, and the continental US. We find that ZIKV circulated undetected in multiple regions for many months before the first locally transmitted cases were confirmed, highlighting the importance of viral surveillance. We identify mutations with possible functional implications for ZIKV biology and pathogenesis, as well as those potentially relevant to the effectiveness of diagnostic tests.

genomics↗