Biology subjects

Jasiulewicz, A.

Publications and source records attributed to Jasiulewicz, A..

4 recordsLinked to original sources

bioRxiv2024

Different vaccine platforms result in distinct antibody responses to the same antigen in haemodialysis patients

Generalised immune dysfunction in chronic kidney disease, especially in patients requiring haemodialysis (HD), significantly enhances the risk of severe infections. Moreover, vaccine-induced immunity is typically reduced in HD populations, but the full mechanisms behind this remain unclear. The SARS-CoV-2 pandemic provided an opportunity to examine the magnitude and functionality of antibody responses in HD patients to a previously unencountered antigen, Spike (S)-glycoprotein, after vaccination with different vaccine platforms (viral vector (VV); mRNA (mRV)). Here, we compared total and functional anti-S antibody responses (cross-variant neutralisation and complement binding) in 187 HD patients and 43 healthy controls 21-28 days after serial immunisation. After 2 doses of the same vaccine, HD patients had anti-S antibody levels and complement binding capacity comparable to controls. However, 2 doses of mRV induced greater polyfunctional antibody responses than VV, yet previous SARS-CoV-2 infection or an mRV boost after 2 doses of VV significantly enhanced antibody functionality in HD patients. Therefore, HD patients can generate near-normal, functional antigen-specific antibody responses following serial vaccination to a novel antigen, suggesting largely intact B cell memory. Encouragingly, exploiting immunological memory by using mRNA vaccines and boosting may improve the success of vaccination strategies in this vulnerable patient population.

immunology↗

bioRxiv2020

A lightweight segmentation and lineage tracking tool for noisy, low frame rate 4D fluorescence microscopy data

4D fluorescence microscopy allows the study of spatiotemporal cell dynamics in embryonic development in unprecedented detail, yet the uneven scattering of light within developing embryos presents challenges in discerning fine details. We present a tool which pre-processes large in vivo 4D microscopy datasets and can then track the movements and lineage histories of rapidly dividing embryonic stem cells. This solution offers a robust, simple segmentation technique to segment high intensity fluorescent features in highly scattered datasets, such as from deep within a developing zebrafish embryo. This tool then offers lineage tracing functionality by tracking rapidly dividing nuclei and their progeny, while also accounting for the jumps rapidly moving features make between frames in low frame rate data. Based on the user having prior knowledge of their imaging subject, this tool has applications in datasets with limitations with signal to noise, and frame rate. It can provide information regarding the position and movement of rapidly dividing nuclei. We demonstrate this pipeline in developing early zebrafish embryos.

bioinformatics↗

bioRxiv2020

Germ plasm localisation dynamics mark distinct phases of transcriptional and post-transcriptional regulation control in primordial germ cells

In many animal models, primordial germ cell (PGC) development depends on maternally-deposited germ plasm to avoid somatic cell fate. Here, we show that PGCs respond to regulatory information from the germ plasm in two distinct phases and mechanisms in zebrafish. We show that PGCs commence zygotic genome activation together with the rest of the embryo with no demonstrable differences in transcriptional and chromatin accessibility levels. Thus, cytoplasmic germ plasm determinants only affect post-transcriptional stabilisation of RNAs to diverge transcriptome from somatic cells, which, unexpectedly, also activate germ cell-specific genes. Perinuclear relocalisation of germ plasm is coupled to dramatic divergence in chromatin opening and transcriptome from somatic cells characterised by PGC-specific chromatin topology. Furthermore, we reveal Tdrd7, regulator of germ plasm localisation, as crucial determinant of germ fate acquisition.

developmental biology↗

bioRxiv2018

A cell cycle-coordinated nuclear compartment for Polymerase II transcription encompasses the earliest gene expression before global genome activation

Most metazoan embryos commence development with rapid cleavages without zygotic gene expression and their genome activation is delayed until the mid-blastula transition (MBT). However, a set of genes escape global repression during the extremely fast cell cycles, which lack gap phases and their transcription is activated before the MBT. Here we describe the formation and the spatio-temporal dynamics of a distinct transcription compartment, which encompasses the earliest detectable transcription during the first wave of genome activation. Simultaneous 4D imaging of expression of pri-miR430 and zinc finger genes by a novel, native transcription imaging approach reveals a pair of shared transcription compartments regulated by homolog chromosome organisation. These nuclear compartments carry the majority of nascent RNAs and transcriptionally active Polymerase II, are depleted of compact chromatin and represent the main sites for detectable transcription before MBT. We demonstrate that transcription occurs in the S-phase of the cleavage cycles and that the gradual slowing of these cell cycles are permissive to transcription before global genome activation. We propose that the demonstrated transcription compartment is part of the regulatory architecture of nucleus organisation, and provides a transcriptionally competent, supporting environment to facilitate early escape from the general nuclear repression before global genome activation.

developmental biology↗