Biology subjects

Baxter, J.

Publications and source records attributed to Baxter, J..

3 recordsLinked to original sources

bioRxiv2018

Principles of Meiotic Chromosome Assembly

During meiotic prophase, chromosomes organise into a series of chromatin loops emanating from a proteinaceous axis, but the mechanisms of assembly remain unclear. Here we elucidate how this elaborate three-dimensional chromosome organisation is underpinned by genomic sequence in Saccharomyces cerevisiae. Entering meiosis, strong cohesin-dependent grid-like Hi-C interaction patterns emerge, reminiscent of mammalian interphase organisation, but with distinct regulation. Meiotic patterns agree with simulations of loop extrusion limited by barriers, yet are patterned by convergent transcription rather than binding of the mammalian interphase factor, CTCF, which is absent in S. cerevisiae--thereby both challenging and extending current paradigms of local chromosome organisation. While grid-like interactions emerge independently of meiotic chromosome synapsis, synapsis itself generates additional compaction that matures differentially according to telomere proximity and chromosome size. Collectively, our results elucidate fundamental principles of chromosome assembly and demonstrate the essential role of cohesin within this evolutionarily conserved process.

molecular biology↗

bioRxiv2018

Functional Deficits are Explained by Plantarflexor Remodeling Following Achilles Tendon Rupture Repair: Preliminary Findings

Achilles tendon ruptures are painful injuries that often lead to long-term functional deficits. Despite the prevalence of these injuries, the mechanism responsible for limited function has not yet been established. Therefore, the purpose of this study was to present preliminary findings that support a hypothesis that skeletal muscle remodeling is the driving factor of poor outcomes in some patients. Biomechanical and ultrasonography assessments were performed on a patient that presented with poor functional outcomes 2.5 years after a surgically-repaired acute Achilles tendon rupture. Single-leg heel raise function was decreased by 70% in the affected limb while walking mechanics showed no deficits. Ultrasonography revealed that the affected limb had shorter, more pennated, and less thick medial gastrocnemius muscles compared to the unaffected limb. A simple computational model of a maximal-effort plantarflexion contraction was employed to test the implications of muscle remodeling on single-leg heel raise function. Subject-specific fascicle length and pennation measurements explained deficits in ankle work and power that strongly agreed with experimentally measured values using motion capture. These preliminary findings support the hypothesis that skeletal muscle goes extensively remodels in response to a ruptured tendon, which reduces the amount of work and power the joint can generate. This multidisciplinary framework of biomechanical, imaging, and computational modeling provides a unique platform for studying the complex interactions between structure and function in patients recovering from Achilles tendon injuries.

bioengineering↗

bioRxiv2016

Cohesin dependent compaction of mitotic chromosomes

Structural Maintenance of Chromosomes (SMC) protein complexes are key determinants of chromosome conformation. Using Hi-C and polymer modelling, we study how cohesin and condensin, two deeply-conserved SMC complexes, organize chromosomes in budding yeast. The canonical role of cohesins is to co-align sister chromatids whilst condensins generally compact mitotic chromosomes. We find strikingly different roles in budding yeast mitosis. First, cohesin is responsible for compacting mitotic chromosomes arms, independent of and in addition to its role in sister-chromatid cohesion. Cohesin dependent mitotic chromosome compaction can be fully accounted for through cis-looping of chromatin by loop extrusion. Second, condensin is dispensable for compaction along chromosomal arms and instead plays a specialized role, structuring rDNA and peri-centromeric regions. Our results argue that the conserved mechanism of SMC complexes is to form chromatin loops and that SMC-dependent looping is readily deployed in a range of contexts to functionally organize chromosomes.\n\nHighlightsO_LICohesin compacts mitotic chromosomes independently of sister chromatid cohesion.\nC_LIO_LIFormation of cis-loops by loop extrusion fully accounts for cohesin-mediated compaction.\nC_LIO_LICondensin is not required for mitotic chromosome compaction of yeast chromosome arms\nC_LIO_LICondensin has a focused pre-anaphase role at centromeres and rDNA in yeast\nC_LI

genomics↗