Biology subjects

Golczak, M.

Publications and source records attributed to Golczak, M..

3 recordsLinked to original sources

bioRxiv2026

stMCP: Spatial Transcriptomics with a Model Context Protocol Server

Spatial transcriptomics enables high-resolution mapping of gene expression in intact tissues but remains challenging due to complex computational workflows that limit accessibility and reproducibility. Here, we present a Model Context Protocol (MCP) framework enabling natural language-driven spatial transcriptomics analysis. By executing analytical tools locally, this architecture eliminates the need to upload massive datasets to large language models, bypassing high token costs and mitigating data privacy and training risks. The MCP orchestrator interprets intent, dynamically routes requests, maintains session state, and verifies input integrity to ensure reproducible execution. Benchmarking across biological discovery, orchestration accuracy, token usage, and execution time demonstrates robust performance. This architecture establishes a scalable template for AI-native research by standardizing the interface between models and local analytical engines. Rather than replacing bioinformaticians, this framework empowers biologists to independently and comprehensively explore their data, accelerating hypothesis testing, and unlocking broader biological discoveries.

bioinformatics↗

bioRxiv2026

Conformational signatures of native ligand and pharmacochaperone binding in rhodopsin

Rhodopsin misfolding underlies rhodopsin-linked retinitis pigmentosa, and small-molecule pharmacochaperones represent a promising therapeutic strategy. However, the mechanisms by which these compounds interact with and stabilize rhodopsin remain poorly understood. Here, we combine backbone amide hydrogen-deuterium exchange mass spectrometry (amide HDX-MS), histidine-specific HDX (His-HDX), protein structure network (PSN) analysis, molecular docking, and functional spectroscopy to define ligand-induced conformational signatures in this receptor elicited by three non-retinoid small molecules, quercetin, myricetin, and the chromenone CR5, and to compare them with those of the native chromophore 11-cis-retinal. Binding of 11-cis-retinal to ligand-free opsin establishes a benchmark orthosteric conformational signature, characterized by strong backbone HDX protection across TM4-TM7 and adjacent loops, suppression of EX1-like hydrogen-deuterium exchange kinetics at the N-terminal ends of TM1 and TM4, and reorganization of PSN hubs that stabilizes an inactive-state residue interaction network. All three non-retinoid ligands generate HDX footprints that closely track this retinal-induced pattern within the chromophore pocket, consistent with direct orthosteric engagement, but they confer weaker and ligand-specific stabilization. Among them, quercetin most closely reproduces the retinal-like backbone protection and His-HDX microenvironment changes, whereas myricetin and CR5 only partially recapitulate retinal-induced stabilization and redistribute conformational flexibility toward TM1 and intradiscal regions, without fully suppressing EX1-like gating. In addition, all three compounds induce weak cytoplasmic allosteric effects in retinal-bound rhodopsin, indicating secondary interactions in addition to a primary orthosteric mechanism. Together, these results provide the first residue-level experimental framework for understanding the differential pharmacochaperoning capacity of non-retinoid ligands and highlight key conformational principles for future optimization of opsin stabilizers.

biochemistry↗

bioRxiv2023

Efficient ultrasound-mediated drug delivery to orthotopic liver tumors: Direct comparison of doxorubicin-loaded nanobubbles and microbubbles

Liver metastasis is a major obstacle in treating aggressive cancers, and current therapeutic options often prove insufficient. To overcome these challenges, there has been growing interest in ultrasound-mediated drug delivery using lipid-shelled microbubbles (MBs) and nanobubbles (NBs) as promising strategies for enhancing drug delivery to tumors. Our previous work demonstrated the potential of Doxorubicin-loaded C3F8 NBs (hDox-NB, 280 {+/-} 123 nm) in improving cancer treatment in vitro using low-frequency ultrasound. In this study, we investigated the pharmacokinetics and biodistribution of sonicated hDox-NBs in orthotopic rat liver tumors. We compared their delivery and therapeutic efficiency with size-isolated MBs (hDox-MB, 1104 {+/-} 373 nm). Results showed a similar accumulation of hDox in tumors treated with hDox-MBs and unfocused therapeutic ultrasound (hDox-MB+TUS) and hDox-NB+TUS. However, significantly increased apoptotic cell death in the tumor and fewer off-target apoptotic cells in the normal liver were found upon the treatment with hDox-NB+TUS. The tumor-to-liver apoptotic ratio was elevated 9.4-fold following treatment with hDox-NB+TUS compared to hDox-MB+TUS, suggesting that the therapeutic efficacy and specificity are significantly increased when using hDox-NB+TUS. These findings highlight the potential of this approach as a viable treatment modality for liver tumors. By elucidating the behavior of drug-loaded bubbles in vivo, we aim to contribute to developing more effective liver cancer treatments that could ultimately improve patient outcomes and decrease off-target side effects.

bioengineering↗