Presumptive TRP channel CED-11 promotes cell volume decrease and facilitates degradation of apoptotic cells in

Apoptotic cells undergo a series of morphological changes. These changes are dependent on caspase cleavage of downstream targets, but which targets are signifi cant and how they facilitate the death process are not well understood. In Caenorhabditis elegans an increase in the refractility of the dying cell is a hallmark morphological change that is caspase dependent. We identify a presumptive transient receptor potential (TRP) cation channel, CED-11, that acts in the dying cell to promote the increase in apoptotic cell refractility. CED-11 is required for multiple other morphological changes during apoptosis, including an increase in electron density as visualized by electron microscopy and a decrease in cell volume. In ced-11 mutants, the degradation of apoptotic cells is delayed. Mutation of ced-11 does not cause an increase in cell survival but can enhance cell survival in other cell-death mutants, indicating that ced-11 facilitates the death process. In short, ced-11 acts downstream of caspase activation to promote the shrinkage, death, and degradation of apoptotic cells. Keywords: TRP channel; apoptosis; C. elegans; cell volume; apoptotic volume decreaseNational Institutes of Health (U.S.) (Grant T32GM007287

Genetic and molecular studies of cell-autonomous execution during programmed cell death in C. elegans

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2016.Cataloged from PDF version of thesis.Includes bibliographical references.Apoptosis or programmed cell death was originally defined by evolutionarily conserved morphological characteristics that include shrinkage of cell volume and chromatin condensation. Apoptosis functions as a highly controlled mechanism for the elimination of unwanted or damaged cells and is essential for disease prevention. Apoptotic cell death is a cell-autonomous process driven by the caspase family of cysteine proteases. The discovery of the CED-3 caspase in C. elegans led to the paradigm that caspase cleavage of substrates drives cell death and promotes engulfment. While many caspase substrates have been identified, it is not well understood how caspase substrates act to promote cell death and engulfment. The control of caspase activation in C. elegans is conserved among metazoans and involves the interplay of pro and anti-apoptotic BCL-2 and BH3-only family proteins. In C. elegans an increase in apoptotic cell refractility observed by Nomarski optics is one of the hallmark morphological characteristics of apoptosis. We found that the presumptive TRP channel CED-1 1 acts downstream of caspase activation in apoptotic cells to drive the increase in refractility. We discovered that CED-1 1 is also required for a decrease in cell volume and increase in nuclear permeability of apoptotic cells. We showed that CED-1 1 is required for efficient degradation of apoptotic cells and facilitates the death process, suggesting that the decrease in cell volume and/or increase in nuclear permeability could promote the death and degradation of the cell. We conclude that CED-1 1 acts downstream of caspase activation to effect multiple observed changes to apoptotic cells and to facilitate death and degradation. In addition we investigated the anti-apoptotic function of the generally pro-apoptotic BCL-2 homolog CED-9.by Kaitlin B. Driscoll.Ph. D

Training the public health emergency response workforce: a mixed-methods approach to evaluating the virtual reality modality

Objectives To produce and evaluate a novel virtual reality (VR) training for public health emergency responders.Design Following a VR training designed to test key public health emergency responder competencies, a prospective cohort of participants completed surveys rating self-assessed skill levels and perceptions of training methods.Setting The VR training sessions were administered in a quiet room at the US Centers for Disease Control and Prevention (CDC), Atlanta, Georgia.Participants All participants volunteered from a list of CDC emergency international surge responders.Outcome measures Perceived impact of the training on responder skills was self-reported via a Likert 5-point scale questionnaire. Assessments were modelled according to the Expanded Technology Acceptance Model measuring participant perceived usefulness of and intention to use the new technology. Inductive coding of qualitative feedback resulted in the identification of central themes.Results From November 2019 to January 2020, 61 participants were enrolled. Most (98%) participants self-rated above neutral for all skills (mean 4.3; range 1.21–5.00). Regression modelling showed that the perceived ease of use of the VR and ability to produce demonstrable results as likely drivers of further use. Participants agreed that others would benefit from the training (97%), it was representative of actual response scenarios (72%) and they would use lessons learnt in the field (71%). Open-response feedback highlighted feeling being immersed in the training and its utility for public health responders.Conclusions At a time when a trained emergency public health workforce is a critical need, VR may be an option for addressing this gap. Participants’ impressions and feedback, in the setting of their high skill level and experience, highlighted the utility and benefit of using VR to deliver training. Further research is needed to determine skill acquisition through VR training among a pool of future responders with limited to no response experience