Using MitER for 3D analysis of mitochondrial morphology and ER contacts.

We have developed an open-source workflow that allows for quantitative single-cell analysis of organelle morphology, distribution, and inter-organelle contacts with an emphasis on the analysis of mitochondria and mitochondria-endoplasmic reticulum (mito-ER) contact sites. As the importance of inter-organelle contacts becomes more widely recognized, there is a concomitant increase in demand for tools to analyze subcellular architecture. Here, we describe a workflow we call MitER (pronounced "mightier"), which allows for automated calculation of organelle morphology, distribution, and inter-organelle contacts from 3D renderings by employing the animation software Blender. We then use MitER to quantify the variations in the mito-ER networks of Saccharomyces cerevisiae, revealing significantly more mito-ER contacts within respiring cells compared to fermenting cells. We then demonstrate how this workflow can be applied to mammalian systems and used to monitor mitochondrial dynamics and inter-organelle contact in time-lapse studies.

Lights up on organelles: Optogenetic tools to control subcellular structure and organization.

Since the neurobiological inception of optogenetics, light-controlled molecular perturbations have been applied in many scientific disciplines to both manipulate and observe cellular function. Proteins exhibiting light-sensitive conformational changes provide researchers with avenues for spatiotemporal control over the cellular environment and serve as valuable alternatives to chemically inducible systems. Optogenetic approaches have been developed to target proteins to specific subcellular compartments, allowing for the manipulation of nuclear translocation and plasma membrane morphology. Additionally, these tools have been harnessed for molecular interrogation of organelle function, location, and dynamics. Optogenetic approaches offer novel ways to answer fundamental biological questions and to improve the efficiency of bioengineered cell factories by controlling the assembly of synthetic organelles. This review first provides a summary of available optogenetic systems with an emphasis on their organelle-specific utility. It then explores the strategies employed for organelle targeting and concludes by discussing our perspective on the future of optogenetics to control subcellular structure and organization. This article is categorized under: Metabolic Diseases > Molecular and Cellular Physiology.

Optogenetics and biosensors set the stage for metabolic cybergenetics.

Cybergenetic systems use computer interfaces to enable feed-back controls over biological processes in real time. The complex and dynamic nature of cellular metabolism makes cybergenetics attractive for controlling engineered metabolic pathways in microbial fermentations. Cybergenetics would not only create new avenues of research into cellular metabolism, it would also enable unprecedented strategies for pathway optimization and bioreactor operation and automation. Implementation of metabolic cybergenetics, however, will require new capabilities from actuators, biosensors, and control algorithms. The recent application of optogenetics in metabolic engineering, the expanding role of genetically encoded biosensors in strain development, and continued progress in control algorithms for biological processes suggest that this technology will become available in the not so distant future.

Data Analysis of Infection Rates Among Exposed Healthcare Workers Could Reveal Effective Prophylactics Against SARS-CoV-2.

The global crisis provoked by the SARS-CoV-2 pandemic, and the economic and social consequences associated to the essential policies applied to contain it, necessitates the expedited development of therapeutic solutions. It is a priority to produce data both rapidly and accurately in order to identify current therapies that can be repurposed to offer protection from SARS-CoV-2 infection. As healthcare workers are both at high risk for infection and able to be readily diagnosed, they offer a potential wealth of data to be analyzed. A systematic data analysis of exposure and infection rates among healthcare workers could yield patterns identifying common protective factors, such as medications with prophylactic potential against SARS-CoV-2, that can be fast-tracked into available therapies. With results suggesting their activity against other coronaviruses and their widespread adoption, Antiretroviral cocktails could be a promising initial target for such large-scale data analysis approach.