arXiv subjects

Sviatlana Shashkova

Publications and source records attributed to Sviatlana Shashkova.

4 recordsLinked to original sources

arXiv2026

Protein Dynamics Beyond Structure Prediction

The ability to predict protein three-dimensional structures from amino acid sequences is a landmark achievement in molecular biology, where recent deep learning approaches such as AlphaFold are the culmination of decades of work. Yet, the quantitative understanding of how protein sequences give rise to dynamic conformational changes and higher-order assemblies remains unsolved. Folding and conformational states are dynamic, stochastic processes, shaped by sequence, energy, co-translational constraints, chaperone machineries, and the physicochemical conditions of the cellular environment. Recent advances now position the field to move beyond static structural endpoints toward a mechanistic understanding of folding dynamics in living systems. Single-molecule techniques enable time-resolved observation of folding trajectories and intermediate states hitherto hidden by traditional structural biology approaches, while computational innovations and data-driven approaches offer new ways to integrate heterogeneous data across scales. In this Roadmap, we review the current conceptual landscape of protein folding, examine the experimental and theoretical gaps that remain, and discuss emerging strategies that integrate high-resolution measurements with multiscale modeling. We outline a roadmap toward a quantitative and predictive science of protein folding dynamics, conformational kinetics, and macromolecular self-assembly. Realizing this vision would transform our understanding of the dynamics of molecular self-organization, from the folding of individual polypeptides to the emergence of dynamic macromolecular complexes. This will enable rational control of folding and misfolding in health and disease, extend protein engineering principles beyond static structural design, and establish a mechanistic foundation for predictive and personalized interventions in proteostasis-related disorders.

q-bio.BM↗

arXiv2026

Technological Excellence Requires Human and Social Context

Breakthrough technologies increasingly shape social institutions, economic systems, and political futures. Yet models of research excellence associated with such technologies often prioritize technical performance, scalability, and short-term innovation metrics while treating ethical, social, and cultural dimensions as secondary considerations. This perspective article argues that such separation is no longer tenable. We propose a broader understanding of excellence that combines technical rigor with ethical robustness, social intelligibility, and long-term relevance. The rapid emergence of generative and agentic artificial intelligence further underscores this argument. As technological systems increasingly operate through language, interpretation, and normative alignment, expertise traditionally cultivated in the humanities and social sciences becomes integral to the design, governance, and responsible deployment of such systems. Drawing on historical examples and contemporary research practices, this article examines five interconnected domains where the humanities and social sciences, treated as integrated dimensions of research practice, can strengthen technological development: (1) ethical, legal, and social integration in agenda-setting and research design; (2) plural and reflexive foresight practices that shape technological futures; (3) graduate education as a leverage point for cross-disciplinary literacy; (4) visualization and communication as epistemic and civic practices; and (5) institutional frameworks that move beyond rigid distinctions between basic and applied research. Across these dimensions, we propose practical strategies for embedding interdisciplinary collaboration structurally rather than symbolically.

physics.soc-ph↗

arXiv2020

Molecular crowding in single eukaryotic cells: using cell environment biosensing and single-molecule optical microscopy to probe dependence on extracellular ionic strength, local glucose conditions, and sensor copy number

The physical and chemical environment inside cells is of fundamental importance to all life but has traditionally been difficult to determine on a subcellular basis. Here we combine cutting-edge genomically integrated FRET biosensing to readout localized molecular crowding in single live yeast cells. Confocal microscopy allows us to build subcellular crowding heatmaps using ratiometric FRET, while whole-cell analysis demonstrates crowding is reduced when yeast is grown in elevated glucose concentrations. Simulations indicate that the cell membrane is largely inaccessible to these sensors and that cytosolic crowding is broadly uniform across each cell over a timescale of seconds. Millisecond single-molecule optical microscopy was used to track molecules and obtain brightness estimates that enabled calculation of crowding sensor copy numbers. The quantification of diffusing molecule trajectories paves the way for correlating subcellular processes and the physicochemical environment of cells under stress.

q-bio.CB↗

arXiv2017

Transcription factor clusters regulate genes in eukaryotic cells

Transcription is regulated through binding factors to gene promoters to activate or repress expression, however, the mechanisms by which factors find targets remain unclear. Using single-molecule fluorescence microscopy, we determined in vivo stoichiometry and spatiotemporal dynamics of a GFP tagged repressor, Mig1, from a paradigm signaling pathway of Saccharomyces cerevisiae. We find the repressor operates in clusters, which upon extracellular signal detection, translocate from the cytoplasm, bind to nuclear targets and turnover. Simulations of Mig1 configuration within a 3D yeast genome model combined with a promoter-specific, fluorescent translation reporter confirmed clusters are the functional unit of gene regulation. In vitro and structural analysis on reconstituted Mig1 suggests that clusters are stabilized by depletion forces between intrinsically disordered sequences. We observed similar clusters of a co-regulatory activator from a different pathway, supporting a generalized cluster model for transcription factors that reduces promoter search times through intersegment transfer while stabilizing gene expression.

q-bio.BM↗