Communications Biophysics

Contains reports on five research projects.National Institutes of Health (Grant 5 P01 GM14940-03)National Institutes of Health (Grant 5 TOl GM01555-03)National Aeronautics and Space Administration (Grant NGL 22-009-304

A Switch from a Gradient to a Threshold Mode in the Regulation of a Transcriptional Cascade Promotes Robust Execution of Meiosis in Budding Yeast

Tight regulation of developmental pathways is of critical importance to all organisms, and is achieved by a transcriptional cascade ensuring the coordinated expression of sets of genes. We aimed to explore whether a strong signal is required to enter and complete a developmental pathway, by using meiosis in budding yeast as a model. We demonstrate that meiosis in budding yeast is insensitive to drastic changes in the levels of its consecutive positive regulators (Ime1, Ime2, and Ndt80). Entry into DNA replication is not correlated with the time of transcription of the early genes that regulate this event. Entry into nuclear division is directly regulated by the time of transcription of the middle genes, as premature transcription of their activator NDT80, leads to a premature entry into the first meiotic division, and loss of coordination between DNA replication and nuclear division. We demonstrate that Cdk1/Cln3 functions as a negative regulator of Ime2, and that ectopic expression of Cln3 delays entry into nuclear division as well as NDT80 transcription. Because Ime2 functions as a positive regulator for premeiotic DNA replication and NDT80 transcription, as well as a negative regulator of Cdk/Cln, we suggest that a double negative feedback loop between Ime2 and Cdk1/Cln3 promotes a bistable switch from the cell cycle to meiosis. Moreover, our results suggest a regulatory mode switch that ensures robust meiosis as the transcription of the early meiosis-specific genes responds in a graded mode to Ime1 levels, whereas that of the middle and late genes as well as initiation of DNA replication, are regulated in a threshold mode

Genetic Identification of a Network of Factors that Functionally Interact with the Nucleosome Remodeling ATPase ISWI

Nucleosome remodeling and covalent modifications of histones play fundamental roles in chromatin structure and function. However, much remains to be learned about how the action of ATP-dependent chromatin remodeling factors and histone-modifying enzymes is coordinated to modulate chromatin organization and transcription. The evolutionarily conserved ATP-dependent chromatin-remodeling factor ISWI plays essential roles in chromosome organization, DNA replication, and transcription regulation. To gain insight into regulation and mechanism of action of ISWI, we conducted an unbiased genetic screen to identify factors with which it interacts in vivo. We found that ISWI interacts with a network of factors that escaped detection in previous biochemical analyses, including the Sin3A gene. The Sin3A protein and the histone deacetylase Rpd3 are part of a conserved histone deacetylase complex involved in transcriptional repression. ISWI and the Sin3A/Rpd3 complex co-localize at specific chromosome domains. Loss of ISWI activity causes a reduction in the binding of the Sin3A/Rpd3 complex to chromatin. Biochemical analysis showed that the ISWI physically interacts with the histone deacetylase activity of the Sin3A/Rpd3 complex. Consistent with these findings, the acetylation of histone H4 is altered when ISWI activity is perturbed in vivo. These findings suggest that ISWI associates with the Sin3A/Rpd3 complex to support its function in vivo

Good Practices in the Co-Production of Knowledge: Working Well Together in Environmental Change Research

This living document proposes good relational practices to support climate change researchers in and beyond the Columbia University Climate School in their efforts to pursue and practice knowledge co-production in their climate-related scholarship, research, and practice. For the purpose of this document, climate researchers are anyone from any background who contributes, in any form, to enhancing our shared understanding, strategies, and responses to climate change. Although this document is focused on research, it also importantly provides communities (Indigenous and non-Indigenous alike), private sector organizations, and others who are carrying out and connected to climate-related work a window into how climate researchers might interact with them, how they can further advocate on their own behalf through the language and aspirations of co-production, and how they can anticipate interacting with researchers through co-production relational way. The document starts with a brief introduction and description of what it does and does not intend to communicate. It then transitions into a framework for good relational practices in knowledge co-production generated through an extensive review of co-production literature in the climate sciences, one-on-one conversations with 9 Columbia University affiliated researchers and practitioners, and a 2.5 day convening with 36 contributors, including Columbia researchers, Indigenous leaders, government representatives, the private sector, and external academics. The framework brings together 28 relational principles and 22 recommended good relational practices, which are summarized under the framework section. The principles and practices are then filtered into 30 reflexive questions, or points of reflection, climate researchers can ask themselves to help use and learn from the good relational practices. The principles, good practices and points of reflection are categorized into 6 interrelated pillars of co-production: The people theme brings attention to the ways in which individual and group identities shape the direction of knowledge co-production efforts. The purpose theme represents the meanings and motivations associated with knowledge co-production. The power theme refers to how power and power relations are understood and enacted through and around efforts to co-produce knowledge. The politics theme centers on the effects of policies and politics on knowledge co-production work at different scales. The pathways theme focuses on tools, approaches, and strategies used to co-produce knowledge in relevant, rigorous, and meaningful ways. The progress theme embodies the broad aspiration that knowledge co-production will catalyze transformative change, whether societal, scientific, cultural, or otherwise. The guidelines are followed with two sections about the motivations for this document and a condensed overview of the history and development of co-production within the environmental and climate sciences. The last section, Steps towards ‘good relational practices’, details how information was gathered and summarized for this document. Drawing from this information, climate researchers are encouraged to use, learn from, and reflect on the information in this document to consider why and how knowledge co-production may or may not be appropriate for their climate-related research

Soundscapes: Toward a Sounded Anthropology

A generation of scholars in multiple disciplines has investigated sound in ways that are productive for anthropologists. We introduce the concept of soundscape as a modality for integrating this work into an anthropological approach. We trace its history as a response to the technological mediations and listening practices emergent in modernity and note its absence in the anthropological literature. We then trace the history of technology that gave rise to anthropological recording practices, film sound techniques, and experimental sound art, noting productive interweavings of these threads. After considering ethnographies that explore relationships between sound, personhood, aesthetics, history, and ideology, we question sound's supposed ephemerality as a reason for the discipline's inattention. We conclude with a call for an anthropology that more seriously engages with its own history as a sounded discipline and moves forward in ways that incorporate the social and cultural sounded world more fully. Copyright © 2010 by Annual Reviews. All rights reserved