Biology subjects

Yurchenko, A.

Publications and source records attributed to Yurchenko, A..

4 recordsLinked to original sources

bioRxiv2026

DNA-GUARD: molecular access control as a physical security layer for DNA data storage

DNA data storage offers exceptional density and millennial-scale stability, with advances in encoding schemes and reduced synthesis costs making large-scale archiving increasingly viable. However, while efforts have focused on reliable data retrieval, securing DNA-encoded information against unauthorized access remains largely unexplored. Here, we introduce DNA-GUARD (DNA Gated Unlocking and Access Restriction of Data), a molecular-level access control system that physically restricts data retrieval rather than relying on computational encryption. DNA-GUARD integrates with PCR-based random access by selectively blocking amplification of protected sequences. Chemically modified "locker strands" outcompete PCR primers and block polymerase extension through 3 inverted dT modifications, preventing amplification of key sequences required for file decoding. To restore access, complementary "password strands" tethered to magnetic particles sequester locker strands, enabling their removal and restoring data access. We demonstrate DNA-GUARDs scalability from 550-byte to 1-MB files without performance loss, orthogonal control of multiple files within mixed libraries, and reliable repeated locking-unlocking cycles. This approach enables physical access control compatible with established DNA storage workflows, providing a foundation for secure archival storage with implications for molecular information security that complements cryptographic data protection methods.

synthetic biology↗

bioRxiv2024

Unveiling DNA Origami Interaction Dynamics on Living Cell Surfaces by Single Particle Tracking

Due to the unique spatial addressability of DNA origami, targeting ligands (e.g. aptamers or antibodies) can be specifically positioned onto the surface of the nanostructure, constituting an essential tool for studying ligand-receptor interactions at the cell surface. While the design and ligand incorporation into DNA origami nanostructures are well-established, the study of cell surface interaction dynamics is still in the explorative phase, where in depth fundamental understanding on the molecular interactions remains underexplored. This study uniquely captures real-time encounters between DNA origami and cells in-situ using single particle tracking (SPT). Here, we functionalized DNA nanorods (NRs) with antibodies or aptamers specific to the epidermal growth factor receptor (EGFR) and used them to target EGFR-overexpressing cancer cells. SPT data revealed that ligand coated NRs selectively bound to the receptors expressed in target cancer cells, while non-functionalized NRs only display negligible cell interactions. Furthermore, we explored the effect of ligand density on the DNA origami, which revealed that aptamer-decorated NRs exhibit non-linear binding characteristics, whereas this effect in antibody-decorated NRs was less pronounced. This study provides new mechanistic insights into the fundamental understanding of DNA origami behaviour at the cell interface, with unprecedented spatiotemporal resolution, aiding the rational design of ligand-targeted DNA origami for biomedical applications.

bioengineering↗

bioRxiv2019

RAS mutations drive proliferative chronic myelomonocytic leukemia via activation of a novel KMT2A-PLK1 axis

ABSTRACTChronic myelomonocytic leukemia (CMML) is an aggressive hematological malignancy with limited treatment options. Whole exome (WES) and targeted sequencing of several independent cohorts of CMML patients, comparing dysplastic (dCMML) to proliferative (pCMML) CMML, as well as paired chronic phase disease and acute leukemic transformation (LT), associate acquisition of oncogenic RAS pathway mutations, the most common being NRASG12D, with aggressive disease and with disease progression. Using patient derived progenitor colony assays and a NRASG12D-Vav-Cre mouse model, we further demonstrate the role of mutant RAS signaling in driving and maintaining pCMML phenotype. RNA-sequencing links RAS pathway mutations with an increased expression of genes encoding the mitotic checkpoint kinases PLK1 and WEE1. Further, we dmeoinstrated that non-mutated lysine methyltransferase KMT2A (MLL1) acts as mediator of NRAS-induced PLK1 and WEE1 expression. Finally, we demonstrate the translational value of our findings by showing that pharmacological PLK1 inhibition decreases monocytosis and hepatosplenomegaly while improving hematopoiesis in RAS mutant patient-derived xenografts. Hence, we define severe CMML as oncogenic RAS pathway-enriched malignancies, with a unique gene expression profile regulated by KMT2A, amenable to therapeutic intervention.

cancer biology↗

bioRxiv2018

Convergence in form and function overcomes non-parallel evolutionary histories in Arctic charr

Understanding the extent to which evolution is predictable under multifarious selection is a longstanding question in evolutionary biology. However, the interplay of stochastic and contingent factors influencing the extent of parallelism in nature is not well understood. To test the predictability of evolution, we studied a natural experiment on different organismal levels across lakes and evolutionary lineages of a freshwater salmonid fish, Arctic charr (Salvelinus alpinus). We identified significant phenotypic parallelism between Arctic charr ecotype pairs within a continuum of parallel evolution and highly parallel adaptive morphological traits. Variability in phenotypic predictability was explained by complex demographic histories, differing genomic backgrounds and genomic responses to selection, variable genetic associations with ecotype, and environmental variation. Remarkably, gene expression was highly similar across ecotype replicates, and explained the observed parallelism continuum. Our findings suggest that parallel evolution by non-parallel evolutionary routes is possible when the regulatory molecular phenotype compensates for divergent histories.

evolutionary biology↗