bioRxiv Science⌕ Search

Biology subjects

Mirza, Z.

Publications and source records attributed to Mirza, Z..

3 recordsLinked to original sources

Co-Designing Research Priorities in Developmental Neuroscience: A Community-Based Participatory Approach

Children and adolescents, the primary participants in developmental neuroscience research, are rarely consulted or included in the research design process. By neglecting their perspectives and needs, we risk limiting the relevance and effectiveness of translational research that may emerge from this work. Here, we report on a process of co-design with adolescents to inform the generation of a new population neuroimaging research programme. We employed a two-study community-based participatory approach and used mixed methods to identify the research priorities of this community. In the first study, 79 secondary school students from four schools were introduced to fundamental neuroscience concepts during five one-hour workshops. In groups, they then designed research studies, centred around topics they deemed important, and were asked to present their ideas through poster presentations, role playing as neuroscientists. Reflexive thematic analysis was conducted on these posters, extracting ten key themes. In the second study, 376 students from four different schools, ranked these ten themes in order of importance. Mental health and stress consistently emerged as the highest priorities. Further exploratory analysis revealed that the priority for exploring everyday routines and understanding anti-social behaviours varied across schools and age groups, while the importance of mental health varied significantly between genders. This work provides an illustration of how to implement place-based participatory approaches at the early stages of a developmental neuroscience research project to maximise inclusivity and potential downstream translation and impact.

neuroscience↗

WormPaths: Caenorhabditis elegans metabolic pathway annotation and visualization

In our group, we aim to understand metabolism in the nematode Caenorhabditis elegans and its relationships with gene expression, physiology and the response to therapeutic drugs. On March 15, 2020, a stay-at-home order was put into effect in the state of Massachusetts, USA, to flatten the curve of the spread of the novel SARS-CoV2 virus that causes COVID-19. For biomedical researchers in our state, this meant putting a hold on experiments for nine weeks until May 18, 2020. To keep the lab engaged and productive, and to enhance communication and collaboration, we embarked on an in-lab project that we all found important but that we never had the time for: the detailed annotation and drawing of C. elegans metabolic pathways. As a result, we present WormPaths, which is composed of two parts: 1) the careful manual annotation of metabolic genes into pathways, categories and levels, and 2) 66 pathway maps that include metabolites, metabolite structures, genes, reactions, and pathway connections between maps. These maps are available on our WormFlux website. We show that WormPaths provides easy-to-navigate maps and that the different levels in WormPaths can be used for metabolic pathway enrichment analysis of transcriptomic data. In the unfortunate event of additional lockdowns, we envision further developing these maps to be more interactive, with an analogy of road maps that are available on mobile devices.

genetics↗

Recombinant Paraprobiotics as a New Paradigm for Treating Gastrointestinal Nematode Parasites of Humans

Gastrointestinal nematodes (GINs) of humans, e.g., hookworms, negatively impact childhood growth, cognition, nutrition, educational attainment, income, productivity, and pregnancy. Hundreds of millions of people are targeted with mass drug administration (MDA) of donated benzimidazole (BZ) anthelmintics. However, BZ efficacy against GINs is suboptimal, and reduced/low efficacy has been seen. Developing an anthelmintic for human MDA is daunting: it must be safe, effective, inexpensive, stable without a cold chain, and massively scalable. Bacillus thuringiensis (Bt) crystal protein 5B (Cry5B) has anthelmintic properties that could fill this void. Here we develop an API (Active Pharmaceutical Ingredient) form of Bt Cry5B compatible with MDA. We expressed Cry5B in asporogenous Bt during vegetative phase, forming cytosolic crystals. These Bacteria with Cytosolic Crystals (BaCC) were rendered inviable (inactivated BaCC or IBaCC) with food-grade essential oils. IBaCC potency was validated in vitro against nematodes. IBaCC was also potent in vivo against human hookworm infections in hamsters. IBaCC production was successfully scaled to 350 liters at a contract manufacturing facility. A simple fit-for-purpose formulation to protect against stomach digestion and powdered IBaCC were successfully made and used against GINS in hamsters and mice. A pilot histopathology study and blood chemistry workup showed that five daily consecutive doses of 200 mg/kg Cry5B IBaCC (the curative single dose is 40 mg/kg) was non-toxic and completely safe. IBaCC is a safe, inexpensive, highly effective, easy-to-manufacture, and scalable anthelmintic that is practical for MDA and represents a new paradigm for treating human GINs.

microbiology↗