Biology subjects

Yoo, M.

Publications and source records attributed to Yoo, M..

3 recordsLinked to original sources

bioRxiv2026

Mapping ortholog-restricted ligandable cysteines in the wheat pathogen Zymoseptoria tritici

Zymoseptoria (Z.) tritici is the fungal phytopathogen responsible for Septoria tritici leaf blotch (STB), the main foliar disease of wheat. Fungicides mitigate crop loss caused by STB, but multidrug-resistant Z. tritici strains pose a major threat to the global food supply and underscore the need to identify new fungicidal targets. Here, we use activity-based protein profiling to generate a covalent ligandability map of Z. tritici, leading to the discovery of cysteines in a diverse set of essential proteins that are targeted by stereochemically defined, electrophilic small molecules (stereoprobes). We identify stereoprobes that display nucleotide-dependent reactivity with an ortholog-restricted cysteine in the GTPase SAR1, leading to accumulation of this protein and other COPII components at apparent ER exit sites and corresponding impairments in Z. tritici growth. Our findings thus expand the scope of ligandable, essential proteins in Z. tritici and illuminate opportunities to selectively target this destructive plant pathogen.

biochemistry↗

bioRxiv2026

Systemic and Local Delivery of siRNA to the CNS and Periphery via Anti-IGF1R Antibody Conjugation

siRNA delivery platforms capable of accessing both central and peripheral tissues are critically needed to expand the therapeutic potential of oligonucleotides. To address this, we developed a novel siRNA-antibody conjugate by attaching an Hprt-targeting siRNA to an engineered antibody shuttle. This shuttle targets the insulin-like growth factor 1 receptor (IGF1R) using a fused antibody fragment (Clone F) and utilizes an antibody backbone with no tissue-relevant binding in this study. The resulting conjugate, designated Clone F-Hprt, demonstrated robust in vivo knockdown across multiple tissues. Clone F-Hprt demonstrated enhanced penetration into central nervous system (CNS) tissues compared to unconjugated siRNA following intracerebroventricular (ICV) and intravenous (IV) administration. In peripheral tissues, Clone F-Hprt achieved widespread knockdown in muscle, heart, and lung, consistent with IGF1R expression. The conjugate was well tolerated across all routes, including with repeated dosing. Although several receptor-mediated approaches for CNS delivery are progressing to the clinic (e.g., targeting the transferrin receptor), clinical validation remains to be demonstrated. Our findings highlight IGF1R as an alternative receptor capable of supporting delivery across both central and peripheral tissues, offering a complementary strategy for expanding the therapeutic landscape of oligonucleotide delivery.

neuroscience↗

bioRxiv2024

Short-term memory errors are strongly associated with a drift in neural activity in the posterior parietal cortex

Understanding the neural mechanisms behind short-term memory (STM) errors is crucial for unraveling cognitive processes and addressing deficits associated with neuropsychiatric disorders. This study examines whether STM errors arise from misrepresentation of sensory information or decay in these representations over time. Using 2-photon calcium imaging in the posterior parietal cortex (PPC) of mice performing a delayed match-to-sample task, we identified a subset of PPC neurons exhibiting both directional and temporal selectivity. Contrary to the hypothesis that STM errors primarily stem from mis-encoding during the sample phase, our findings reveal that these errors are more strongly associated with a drift in neural activity during the delay period. This drift leads to a gradual divergence away from the correct representation, ultimately leading to incorrect behavioral responses. These results emphasize the importance of maintaining stable neural representations in the PPC for accurate STM. Furthermore, they highlight the potential for therapeutic interventions aimed at stabilizing PPC activity during delay periods as a strategy for mitigating cognitive impairments in conditions like schizophrenia.

animal behavior and cognition↗