[
Autophagy,
2024]
Professor Richard (Rick) Morimoto is the Bill and Gayle Cook Professor of Biology and Director of the Rice Institute for Biomedical Research at Northwestern University. He has made foundational contributions to our understanding of how cells respond to various stresses, and the role played in those responses by chaperones. Working across a variety of experimental models, from <i>C</i>. <i>elegans</i> to human neuronal cells, he has identified a number of important molecular components that sense and respond to stress, and he has dissected how stress alters cellular and organismal physiology. Together with colleagues, Professor Morimoto has coined the term "proteostasis" to signify the homeostatic control of protein expression and function, and in recent years he has been one of the leaders of a consortium trying to understand proteostasis in healthy and disease states. I took the opportunity to talk with Professor Morimoto about proteostasis in general, the aims of the consortium, and how autophagy is playing an important role in their research effort.
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Philos Trans R Soc Lond B Biol Sci,
2018]
Control is essential to the functioning of any neural system. Indeed, under healthy conditions the brain must be able to continuously maintain a tight functional control between the system's inputs and outputs. One may therefore hypothesize that the brain's wiring is predetermined by the need to maintain control across multiple scales, maintaining the stability of key internal variables, and producing behaviour in response to environmental cues. Recent advances in network control have offered a powerful mathematical framework to explore the structure-function relationship in complex biological, social and technological networks, and are beginning to yield important and precise insights on neuronal systems. The network control paradigm promises a predictive, quantitative framework to unite the distinct datasets necessary to fully describe a nervous system, and provide mechanistic explanations for the observed structure and function relationships. Here, we provide a thorough review of the network control framework as applied to <i>Caenorhabditis elegans</i> (Yan <i>et al.</i> 2017 <i>Nature</i><b>550</b>, 519-523. (doi:10.1038/nature24056)), in the style of Frequently Asked Questions. We present the theoretical, computational and experimental aspects of network control, and discuss its current capabilities and limitations, together with the next likely advances and improvements. We further present the Python code to enable exploration of control principles in a manner specific to this prototypical organism.This article is part of a discussion meeting issue 'Connectome to behaviour: modelling <i>C. elegans</i> at cellular resolution'.
[
Methods Cell Biol,
1995]
ACeDB (A Caenorhabditis elegans Data Base) is a data management and display system that contains a wide range of genomic and other information about C. elegans. This chapter provides an overview of ACeDB for the C. elegans user, focusing in particular on the Macintosh version Macace. Previous reviews of AceDB include those of Thierry-Mieg and Durbin (1992) and Durbin and Thierry-Mieg (1994), which describe the general properties of the whole system, and that by Dunham et al. (1994), which discussed the use of AceDB for physical map data collection and assembly. ACeDB was developed by Jean Thierry-Mieg and Richard Durbin primarily for the C. elegans project, when the genomic sequencing project was just beginning in 1990. The original aim was to create a single database that integrated the genetic and physical maps with both genomic sequence data and the literature references. The forerunner of ACeDB was the program CONTIG9 (Sulston et al., 1988), which was developed to maintain and edit the physical map. CONTIG9 served researchers around the world by providing critical on-line access to the current physical map as it was being constructed (Coulson et al., 1986). This policy of immediate access allowed members of the worm community to see the same data as the people making the map, and proved very successful in maximizing use of the map. The same approach was adopted as a template for ACeDB. These two principles, developing a comprehensive database for all types of genomic and related data and providing public access to the data in the same form as used by the data-collecting laboratories, have continued to underlie developments of ACeDB. Over the last 5 years, a wide range of genome projects relating to other organisms have taken the ACeDB program and used it to develop databases for their own data. ACeDB has been used both in public projects designed to redistribute public data in a coordinated fashion and laboratory-based projects for collecting new data. Others, such as the C. elegans ACeDB, have used the database for both purposes. The reason it has been possible to adapt ACeDB so widely is that its flexible data structure allows new types of objects and new types of information about these objects to be added easily. This chapter describes (1) how to obtain ACeDB and documentation for it, (2) how to access and use the information in ACeDB, and (3) how to use ACeDB as a laboratory-based data managing system. Some of what we discuss is specific to the nematode database, but other information applies to the basic computer software program and, hence, to any database using the ACeDB program.