Biology subjects

Turunen, P.

Publications and source records attributed to Turunen, P..

3 recordsLinked to original sources

bioRxiv2026

Anterior insular CB1 receptor signaling selectively regulates social novelty and anxiety-related behaviors

Several neurodevelopmental disorders (NDDs) are characterized by impairments in social behavior and affective dysregulation. Converging evidence implicates the endocannabinoid system in the control of both behaviors. However, the brain region-specific contribution of cannabinoid receptor type 1 (CB1R) signaling to these NDD-relevant phenotypes remains unclear. The anterior insular cortex (aINS) is a key integrative hub involved in socio-emotional processing and social novelty recognition. Whether CB1Rs within this region are sufficient to regulate behavioral domains disrupted in NDDs remains unclear. Here, we employed a Cre-dependent viral strategy to selectively restore CB1R mRNA expression in the aINS of global CB1R-deficient mice. Region-specific rescue of CB1R in the aINS normalized social novelty discrimination and reduced anxiety-like behavior as compared to mice lacking CB1R, while leaving basal sociability and locomotor activity unaffected. In addition, insular CB1R re-expression modulated repetitive-like behaviors without broadly altering other behavioral domains. These effects were observed in the absence of off-target expression, supporting the specificity of the genetic manipulation. Our findings demonstrate that CB1R mRNA expression within the aINS is sufficient to regulate distinct socio-emotional and repetitive behavioral domains. These results identify the aINS as a critical CB1-dependent modulatory node and provide mechanistic insight into how region-specific endocannabinoid signaling contributes to behavioral phenotypes relevant to NDDs.

neuroscience↗

bioRxiv2024

Tuning non-linear mechanics in collagen hydrogels modulates three dimensional cellular morphotypes

Collagen networks contribute to tissue architecture and modulate cellular responses in crowded three-dimensional environments. Therefore, it is the most widely used biological polymer in three-dimensional studies of cellular interactions with the extracellular matrix. In vivo, collagen exists embedded within additional matrix components. Studies have shown that the combination of matrices induces synergistic mechanical interactions, influencing the non-linear mechanical behaviour of collagen networks. However, how cells respond to changes in collagen non-linear elasticity remains largely unknown. By precisely controlling the mechanical behaviour of collagen networks with the biologically inert and semiflexible polymer polyisocyanopeptides, we demonstrate that changes in the non-linear elasticity of collagen induces morphological cell responses that influence how cells migrate, proliferate, and interact with collagen. We found that when collagen rigidifies in the presence of a second component, this induces morphological changes in cell-matrix interactions, resulting in a decrease in migration and the ability of cells to deform collagen matrices. Our results demonstrate that the onset of collagen stiffening is key to inducing intracellular tension which dictates morphological cell responses in three-dimensional collagen networks. We anticipate our findings will prove useful in understanding how cells respond to changes in collagen mechanics when combined in double network systems which better recapitulates tissues in vivo.

biophysics↗

bioRxiv2024

Identification of unique and potent inhibitors of SARS-CoV-2 main protease from DNA-encoded chemical libraries

In vitro screening of large compounds libraries with automated high-throughput screening is expensive, time consuming and requires dedicated infrastructures. Conversely, the selection of DNA-encoded chemical libraries (DECL) can be rapidly performed with routine equipment available in most laboratories. In this study we identified novel inhibitors of SARS-CoV-2 main protease (Mpro) through the affinity-based selection of the DELopen library (open access for academics), containing 4.2 billion compounds. The identified inhibitors were peptide-like compounds containing an N-terminal electrophilic group able to form a covalent bond with the nucleophilic Cys145 of Mpro, as confirmed by x-ray crystallography. This DECL selection campaign enabled the discovery of the unoptimized compound SLL11 displaying an IC50 of 30 nM, proving that the rapid exploration of large chemical spaces enabled by DECL technology, allows for the direct identification of potent inhibitors avoiding several rounds of iterative medicinal chemistry. Compound MP1, a close analogue of SLL11, showed antiviral activity against SARS-CoV-2 in the low micromolar range when tested in Caco-2 and Calu-3 (EC50 = 2.3 {micro}M) cell lines. As peptide-like compounds can suffer from low cell permeability and metabolic stability, the cyclization of the compounds as well as the substitution of selected residues with D-enantiomers will be explored in the future to improve the antiviral activity of these novel compounds.

microbiology↗