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Kosik, K.

Publications and source records attributed to Kosik, K..

3 recordsLinked to original sources

SpikeLab: Agentic tools for spike data analysis

Large language models have the potential to transform scientific research and analysis, but without domain-specific structure they produce silent methodological errors, unreported decisions, and irreproducible results. Here we present SpikeLab, a text-to-analysis framework for neural spike data that combines composable data structures with a skill-based agentic system enforcing bounded autonomy: mandatory use of expert-vetted methods, correctness over efficiency, and clarification-seeking on ambiguous requests. In a controlled benchmark on electrophysiology data, Sonnet 4.6 with SpikeLab produced correct and reproducible results across all tasks, outperforming both the unassisted Sonnet and the more capable Opus 4.6, which exhibited deterministic failures including ad hoc method invention, silent data reduction, and inconsistent experimental designs. We demonstrate versatility across in vivo mouse, human, and in vitro brain organoid recordings, and apply the framework to a pharmacological dose-response study spanning single-unit dynamics, pairwise network structure, burst-level temporal sequences, and latent population states, all through natural language prompts without writing analysis code.

neuroscience↗

The Proline-rich Domain Promotes Tau Liquid Liquid Phase Separation in Cells

Tau protein in vitro can undergo liquid liquid phase separation (LLPS); however, observations of this phase transition in living cells are limited. To investigate protein state transitions in living cells we found that Cry2 can optogentically increase the association of full lengh tau with microtubules. To probe this mechanism, we identified tau domains that drive tau clustering on microtubules in living cells. The polyproline rich domain (PRD) drives LLPS and does so under the control of phosphorylation. These readily observable cytoplasmic condensates underwent fusion and fluorescence recovery after photobleaching consistent with the ability of the PRD to undergo LLPS in vitro. In absence of the MTBD, the tau PRD co-condensed with EB1, a regulator of plus-end microtubule dynamic instability. The specific domain properties of the MTBD and PRD serve distinct but mutually complementary roles that utilize LLPS in a cellular context to implement emergent functionalities that scale their relationship from binding alpha-beta tubulin heterodimers to the larger proportions of microtubules.

neuroscience↗

A Molecular Signature for Anastasis, Recovery from the Brink of Apoptotic Cell Death

During apoptosis, executioner caspase activity has been considered a point of no return. However, recent studies show that cells can survive caspase activation following transient apoptotic stimuli, a process named anastasis. To identify a molecular signature, we performed whole transcriptome RNA sequencing of untreated, apoptotic, and recovering HeLa cells. We found that anastasis is an active, two-stage program. During the early stage, cells transition from growth-arrested to growing. In the late stage, cells change from proliferating to migratory. Strikingly, some early recovery mRNAs were elevated first during apoptosis, implying that dying cells poise to recover, even while still under apoptotic stress. Furthermore, TGF{beta}-induced Snail expression is required for anastasis, and recovering cells exhibit prolonged elevation of pro-angiogenic factors. This study demonstrates similarities in the anastasis genes, pathways, and cell behaviors to those activated in wound healing. This study identifies a repertoire of potential targets for therapeutic manipulation of this process.

cell biology↗