Biology subjects

Tahir, H.

Publications and source records attributed to Tahir, H..

5 recordsLinked to original sources

bioRxiv2026

Micro-to-Macro Scale Hydrogel Microchannel Networks by Twisted Wire Templating

The human vasculature is a complex, multiscale system comprising hierarchical networks of macroscale to microscopic vessels. Existing in vitro fabrication techniques often fail to bridge these disparate scales, as high-resolution methods like multiphoton ablation are too slow for replicating larger vessels, while 3D printing lacks the resolution for fine microscale features. Here, we report a "twisted wire templating" strategy capable of generating perfusable bifurcating hydrogel networks that seamlessly transition from the macro- to the micro-scale (2.3 mm to 140 {micro}m) through seven orders of bifurcations. By optimizing wire-twisting geometries and polyurethane dip-coating, we overcame instability-driven bead formation to ensure replication fidelity across the networks. Fabrication rigs were reconfigured from existing 2D planar layouts to 3D reconfigurable architectures to better replicate 3D vessel geometries which simultaneously reducing the laboratory footprint and fabrication times by 47%. Using a Taguchi orthogonal array, we further optimized surface chemistry and hydrogel composition to inhibit structural failure during template extraction, resulting in fully patent, perfusable networks. This method provides a robust, low-cost, and scalable foundation for creating physiologically representative vascular models for investigating multiscale disease mechanisms and organ-level tissue engineering.

bioengineering↗

bioRxiv2025

Generation of an optimised Cumate toolkit for tuneable protein expression during in vitro and in vivo studies of Burkholderia cenocepacia

Inducible gene expression is pivotal for dissecting bacterial physiology and virulence mechanisms. Across the Burkholderia genera, a limited range of inducible systems currently exist that show minimal impacts on the proteome and allow tight regulation. In this study, we engineer a set of cumate inducible vectors for use in Burkholderia cenocepacia that offer minimal basal expression and the ability to control B. cenocepacia gene expression within Eukaryotic cells. Through mutagenesis-based studies of cumate circuits and the cumate regulator (CymR), we generate an optimized cumate circuit (PCymRC/CymRGV) which allows the tight and tunable control of protein expression within B. cenocepacia, as assessed by fluorescent and protein O-linked glycosylation analysis. Using comparative proteomics, we demonstrate cumate induction leads to both reduced and orthogonal effects on B. cenocepacia compared to widely used rhamnose based induction systems. Leveraging the cell permeability of cumate and the generation of a CTX-based chromosomal integration vector, we show that inducible control of protein expression is achievable during intracellular replication of B. cenocepacia. Finally, using the ability to control intracellular expression, we demonstrate the requirement of O-linked protein glycosylation for optimal B. cenocepacia intracellular replication. Combined, this work demonstrates that cumate inducible systems allow precise and tuneable gene expression in Burkholderia even within a host-pathogen context. ImportanceThis work establishes optimised cumate-inducible vectors for use in Burkholderia cenocepacia, addressing the need for alternative inducers to available carbohydrate systems. We show cumate-inducible vectors allow precise control of gene expression even within eukaryotic cells, providing a new and orthogonal way to temporally control protein induction. Utilising cumate- based induction, we demonstrate the importance of O-linked protein glycosylation for optimal intracellular replication in B. cenocepacia, highlighting its potential to be used to explore host- pathogen interactions. Combined, this work shows cumate-inducible vectors extend the range of studies which can be undertaken to dissect B. cenocepacia physiology and virulence.

microbiology↗

bioRxiv2024

The Late-Stage Steps of Burkholderia cenocepacia Protein O-Linked Glycan Biosynthesis Are Conditionally Essential.

Periplasmic O-linked protein glycosylation is a highly conserved process observed across the Burkholderia genus. Within Burkholderia, protein glycosylation requires the five gene cluster known as the O-glycosylation cluster (OGC, ogcXABEI) which facilitates the construction of the O-linked trisaccharide attached to periplasmic proteins. Previous studies have reported conflicting results regarding the essentiality of ogcA, predicted to be responsible for the addition of the final carbohydrate of the O-linked trisaccharide and ogcX, the putative O-linked glycan flippase. Within this work, we aimed to dissect the impact of the loss of ogcA and ogcX on Burkholderia cenocepacia viability. We demonstrate that the loss of either ogcA or ogcX are detrimental if glycosylation is initiated leading to marked phenotypic effects. Proteomic analysis supports that the loss of ogcA/ogcX both blocks glycosylation and drives pleotropic effects in the membrane proteome, resulting in the loss of membrane integrity. Consistent with this, strains lacking ogcA and ogcX exhibit increased sensitivity to membrane stressors including antibiotics and demonstrate marked changes in membrane permeability. These effects are consistent with fouling of the undecaprenyl pool due to dead-end O-linked glycan intermediates, and consistent with this, we show that modulation of the undecaprenyl pool through the overexpression of undecaprenyl pyrophosphate synthase (UppS) or the OGC flippase (OgcX) restores viability while expression of early-stage OGC biosynthesis genes (ogcI and ogcB) reduce B. cenocepacia viability. These findings demonstrate disrupting O-linked glycan biosynthesis or transport appears to dramatically impact B. cenocepacia viability, supporting the assignment of ogcA and ogcX as conditionally essential. ImportanceProtein glycosylation, a conserved process in Burkholderia species, utilizes glycans generated by the O-glycosylation cluster (OGC), which is composed of five genes (ogcX, ogcA, ogcB, ogcE, and ogcI). In this study, we demonstrate that the loss of ogcA or ogcX significantly affects the physiology of Burkholderia cenocepacia. Using complementary genetic approaches and proteomic techniques, we show that the loss of ogcA or ogcX blocks glycosylation, alters the cell membrane, and sensitizes cells to stressors such as antibiotics. This increased sensitivity to membrane stress is consistent with the accumulation of dead-end O-linked glycan intermediates, which sequester the limited and essential undecaprenyl pool within B. cenocepacia. These findings highlight that ogcA and ogcX are conditionally essential for B. cenocepacia survival and provides mechanistic insight into how protein glycosylation fidelity--the use of specific glycans for protein glycosylation--is controlled in Burkholderia species.

microbiology↗

bioRxiv2019

Socioeconomic impacts of elimination of Onchocerciasis in Abu-Hamed focus, northern Sudan: lessons after elimination

IntroductionOnchocerciasis is one of the most devastating Neglected Tropical Diseases (NTDs) and it is mostly prevalent in Africa. The disease has important heavy social and economic burdens on the infected populations including low productivity, unemployment, social isolation, and stigma. Methodology/Principal FindingsThe socio-economic impacts of the Onchocerciasis elimination in Abu-Hamed, River Nile State, Sudan; were investigated using a well-established questionnaire, 512 participants in ten affected communities were interviewed. Our findings revealed that these communities are recovering from the social and economic burden of the diseases, with 90% of the research participants reported general satisfaction about the elimination of the disease in their community, and about 48.3% of them attended secondary school or university. Only 0.6% reported unemployment, and 25.3% and 24.7% of the participants were workers and farmers respectively. Except about the vector biting and nuisance, the majority of the respondents (90%) had no complain after the elimination of the disease in the area. Also, 90.5% of the participants reported either stable or increase in their work performance during the last twelve months. About 93.8% of the respondents were engaged in normal daily activities and involved in happy events like marriage and giving birth during the last twelve months. Conclusions/SignificanceOverall, we conclude that the elimination of Onchocerciasis in Abu-Hamed has several positive impacts on the economy and social life of Abu-Hamed local communities, but this could be maximized by controlling the vector, which is still having a negative impact on the populations. Establishing local developmental projects will help these communities greatly to recover and become more productive. Author SummaryOnchocerciasis, also known as the river blindness, is a disease that caused by a parasitic worm which could infest people eyes or skin causing a blindness or sub-dermal disease. This worm is transmitted to human by the bite of an insect, the black fly. Although the disease is not fatal in most of the patient but it presents a significant economic and social burden on the infected people, their families and communities. This burden is a result of the social stigma associated with the skin form of the disease, and the lack of vision in case of blindness (ocular manifestation). Onchocerciasis was a public health problem in the study site, Abu-Hamed. In 2015, the disease was officially has been declared eliminated from the area. We investigated the socio-economic impacts of this success on the local communities. We have interviewed randomly selected 512 participants to understand their perspective and highlighting their experience regarding the disease elimination. Our research aimed to fill the gap of knowledge between the public health and social science by highlighting the social and economic benefits of health interventions and diseases elimination/eradication. Furthermore, to urge intervention programs to empower the local communities in the planning and implementation of health interventions for a better success.

microbiology↗

bioRxiv2017

Mechanical stretching can modify the axial morphology of early chick embryos

Physical cues, experienced during early embryonic development, can influence species-specific vertebral numbers. Here we show that mechanical stretching of live chicken embryos can induce the formation of additional somites and thereby modify early segmental patterning. Stretching deforms the somites, and results in a cellular reorganization that forms stable daughter somites. Cells from the somite core thereby undergo mesenchymal-to-epithelial transitions (MET), thus meeting the geometrical demand for more border cells. Using a Cellular Potts Model, we suggest that this MET occurs through lateral induction by the existing epithelial cells. Our results indicate that self-organizing properties of the somitic mesoderm generate phenotypic plasticity that allows it to cope with variations in the mechanical environment. This plasticity may provide a novel mechanism for explaining how vertebral numbers in species may have increased during evolution. Additionally, by preventing the formation of transitional vertebrae, these self-organization qualities of somites may be selectively advantageous.

developmental biology↗