Biology subjects

Robinson, B. V.

Publications and source records attributed to Robinson, B. V..

3 recordsLinked to original sources

bioRxiv2025

The CPEB ortholog Orb2 regulates brain size through the TRIM-NHL RNA-binding protein, Brain tumor

Neurodevelopment requires precise translational control, the disruption of which is implicated in various neurological disorders, including developmental delays, intellectual disability, and microcephaly. We report a novel role for the Drosophila CPEB-family protein Orb2, a translational regulator, in controlling brain size in a dose dependent manner. Loss of orb2 results in larval brain hypotrophy, whereas orb2 overexpression causes brain overgrowth. We demonstrate that orb2 is required for neural stem cell development from embryonic stages through larval neurogenesis. Structure-function analysis reveals that Orb2 RNA-binding activity promotes brain growth, while its poly-Q and ZZ domains act to restrain overgrowth. Further genetic and biochemical evidence indicates that orb2 functions upstream of the translational repressor Brain tumor (Brat), modulating Brat protein levels and, consequently, influencing brain size. These findings support a model wherein the antagonistic activities of Orb2 and Brat are critical for balanced brain growth during Drosophila neurodevelopment.

developmental biology↗

bioRxiv2024

Cell-free screening, production and animal testing of a STI-related chlamydial major outer membrane protein supported in nanolipoproteins.

Vaccine development against Chlamydia, a prevalent sexually transmitted infection (STI), is imperative due to its global public health impact. However, significant challenges arise in the production of effective subunit vaccine based on recombinant protein antigens, particularly with membrane proteins like the Major Outer Membrane Protein (MOMP). Cell-free protein synthesis (CFPS) technology is an attractive method to address these challenges as a method of high-throughput membrane protein and protein complex production coupled with nanolipoprotein particles (NLPs). NLPs provides a supporting scaffold while allowing easy adjuvant addition during formulation. Over the last decade we have been working toward production and characterization of MOMP-NLP complexes for vaccine testing. The work presented here highlights the expression and biophysical analyses, including transmission electron microscopy (TEM) and dynamic light scattering (DLS), confirm formation and functionality of MOMP-NLP complexes for use in animal studies. Moreover, immunization studies in preclinical models compare the past and present protective efficacy of MOMP-NLP formulations, particularly when co-adjuvanted with CpG and FSL1. Ex vivo assessments further highlight the immunomodulatory effects of MOMP-NLP vaccinations, emphasizing their potential in eliciting robust immune responses. However, further research is warranted to further optimize vaccine formulations, validate efficacy against Chlamydia trachomatis, and better understand underlying mechanisms of immune response.

immunology↗

bioRxiv2021

The RNA-binding protein Orb2 is associated with microcephaly and supports centrosome asymmetry in neural stem cells

To maintain a balance of self-renewal versus neurogenesis, neural stem cells (NSCs) undergo asymmetric cell division along an invariant polarity axis instructed by centrosomes. In the NSCs of the third instar Drosophila larval brain, the interphase centrosomes are defined by marked asymmetries in protein composition and functional activity as microtubule-organizing centers. Here we show that a conserved RNA-binding protein, Orb2, supports NSC centrosome asymmetry by localizing to the cytoplasm, where it promotes robust apical centrosome maturation and transient basal centrosome inactivation, required for centrosome segregation and spindle morphogenesis. Orb2 is required cell autonomously within NSCs to support centrosome asymmetry and maintenance of the stem cell pool. We suggest Orb2 plays opposing roles in centrosome activation and inactivation at the apical versus basal centrosomes respectively, possibly through the translational regulation of multiple mRNAs. Conversely, loss of orb2 manifests in microcephaly independent of Orb2 function in NSCs. Bioinformatics uncovers a significant overlap among RNA targets between Drosophila Orb2 and human CPEB4, consistent with a conserved role for CPEB proteins in centrosome regulation and neurodevelopment.

cell biology↗