ABSTRACT
The complex multistep activation cascade of Ire1 involves changes in the Ire1 conformation and oligomeric state. Ire1 activation enhances ER folding capacity, in part by overexpressing the ER Hsp70 molecular chaperone BiP; in turn, BiP provides tight negative control of Ire1 activation. This study demonstrates that BiP regulates Ire1 activation through a direct interaction with Ire1 oligomers. Particularly, we demonstrated that the binding of Ire1 luminal domain (LD) to unfolded protein substrates not only trigger conformational changes in Ire1-LD that favour the formation of Ire1-LD oligomers but also exposes BiP binding motifs, enabling the molecular chaperone BiP to directly bind to Ire1-LD in an ATP-dependent manner. These transient interactions between BiP and two short motifs in the disordered region of Ire1-LD are reminiscent of interactions between clathrin and another Hsp70, cytoplasmic Hsc70. BiP binding to substrate-bound Ire1-LD oligomers enables unfolded protein substrates and BiP to synergistically and dynamically control Ire1-LD oligomerisation, helping to return Ire1 to its deactivated state when an ER stress response is no longer required.
Subject(s)
Endoplasmic Reticulum Chaperone BiP , Endoplasmic Reticulum Stress , Endoribonucleases , Heat-Shock Proteins , Protein Binding , Protein Serine-Threonine Kinases , Protein Serine-Threonine Kinases/metabolism , Endoplasmic Reticulum Chaperone BiP/metabolism , Heat-Shock Proteins/metabolism , Heat-Shock Proteins/chemistry , Endoribonucleases/metabolism , Endoribonucleases/chemistry , Humans , Endoplasmic Reticulum/metabolism , Unfolded Protein Response , Protein Multimerization , HSP70 Heat-Shock Proteins/metabolism , HSP70 Heat-Shock Proteins/chemistry , Protein Folding , Molecular Chaperones/metabolism , Molecular Chaperones/chemistry , Protein DomainsABSTRACT
In societies without writing, ethnographically known rituals have rarely been tracked back archaeologically more than a few hundred years. At the invitation of GunaiKurnai Aboriginal Elders, we undertook archaeological excavations at Cloggs Cave in the foothills of the Australian Alps. In GunaiKurnai Country, caves were not used as residential places during the early colonial period (mid-nineteenth century CE), but as secluded retreats for the performance of rituals by Aboriginal medicine men and women known as 'mulla-mullung', as documented by ethnographers. Here we report the discovery of buried 11,000- and 12,000-year-old miniature fireplaces with protruding trimmed wooden artefacts made of Casuarina wood smeared with animal or human fat, matching the configuration and contents of GunaiKurnai ritual installations described in nineteenth-century ethnography. These findings represent 500 generations of cultural transmission of an ethnographically documented ritual practice that dates back to the end of the last ice age and that contains Australia's oldest known wooden artefacts.
ABSTRACT
The giant cytoskeletal protein obscurin contains multiple cell signaling domains that influence cell migration. Here, we follow each of these pathways, examine how these pathways modulate epithelial cell migration, and discuss the cross-talk between these pathways. Specifically, obscurin uses its PH domain to inhibit phosphoinositide-3-kinase (PI3K)-dependent migration and its RhoGEF domain to activate RhoA and slow cell migration. While obscurin's effect on the PI3K pathway agrees with the literature, obscurin's effect on the RhoA pathway runs counter to most other RhoA effectors, whose activation tends to lead to enhanced motility. Obscurin also phosphorylates cadherins, and this may also influence cell motility. When taken together, obscurin's ability to modulate three independent cell migration pathways is likely why obscurin knockout cells experience enhanced epithelial to mesenchymal transition, and why obscurin is a frequently mutated gene in several types of cancer.
ABSTRACT
The highly conserved and essential Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) has emerged as the leading target for vaccines against the disease-causing blood stage of malaria. However, the features of the human vaccine-induced antibody response that confer highly potent inhibition of malaria parasite invasion into red blood cells are not well defined. Here, we characterize 236 human IgG monoclonal antibodies, derived from 15 donors, induced by the most advanced PfRH5 vaccine. We define the antigenic landscape of this molecule and establish that epitope specificity, antibody association rate, and intra-PfRH5 antibody interactions are key determinants of functional anti-parasitic potency. In addition, we identify a germline IgG gene combination that results in an exceptionally potent class of antibody and demonstrate its prophylactic potential to protect against P. falciparum parasite challenge in vivo. This comprehensive dataset provides a framework to guide rational design of next-generation vaccines and prophylactic antibodies to protect against blood-stage malaria.
ABSTRACT
The fossil record of parasitism is poorly understood, due largely to the scarcity of strong fossil evidence of parasites. Understanding the preservation potential for fossil parasitic evidence is critical to contextualizing the fossil record of parasitism. Here, we present the first use of X-ray computed tomography (CT) scanning and finite elements analysis (FEA) to analyze the impact of a parasite-induced fossil trace on host preservation. Four fossil and three modern decapod crustacean specimens with branchial swellings attributed to an epicaridean isopod parasite were CT scanned and examined with FEA to assess differences in the magnitude and distribution of stress between normal and swollen branchial chambers. The results of the FEA show highly localized stress peaks in reaction to point forces, with higher peak stress on the swollen branchial chamber for nearly all specimens and different forces applied, suggesting a possible shape-related decrease in the preservation potential of these parasitic swellings. Broader application of these methods as well as advances in the application of 3D data analysis in paleontology are critical to understanding the fossil record of parasitism and other poorly represented fossil groups.
Subject(s)
Decapoda , Isopoda , Parasites , Animals , Paleontology , Fossils , Isopoda/parasitologyABSTRACT
Effective interprofessional team function is integral to high-quality care in the intensive care unit (ICU). However, little is known about how familiarity develops among teams, which may be an important antecedent to effective team function and quality care. To examine team familiarity and how it impacts ICU team function and care, we conducted an ethnographic study in four ICUs (two medical ICUs, one mixed medical-surgical ICU, and one surgical ICU) in two community hospitals and one academic medical center. We conducted 57.5 h of observation, 26 shadowing experiences, and 26 interviews across the four ICUs sequentially. We used thematic analysis to examine familiarity among the team. We found that ICU team members become familiar with their team through interpersonal, relational interactions, which involved communication, time working together, social interactions, trust, and respect. Our findings underscore the relational aspect of effective teams and demonstrate that time working together, social interactions, communication, developing trust, and respect are pathways to familiarity and optimal team function. Leveraging unique and creative ways to enhance the relational aspects of ICU teams could be an area for future research and lead to improved ICU outcomes.
Subject(s)
Anthropology, Cultural , Communication , Intensive Care Units , Interprofessional Relations , Patient Care Team , Trust , Humans , Intensive Care Units/organization & administration , Patient Care Team/organization & administration , Cooperative Behavior , Social Interaction , Female , Male , Respect , Interpersonal Relations , Interviews as TopicABSTRACT
Dominant missense variants in MYBPC1 encoding slow Myosin Binding Protein-C (sMyBP-C) have been increasingly linked to arthrogryposis syndromes and congenital myopathy with tremor. Herein, we describe novel compound heterozygous variants - NM_002465.4:[c.2486_2492del];[c.2663A > G] - present in fibronectin-III (Fn-III) C7 and immunoglobulin (Ig) C8 domains, respectively, manifesting as severe, early-onset distal arthrogryposis type-1, with the carrier requiring intensive care and several surgical interventions at an early age. Computational modeling predicts that the c.2486_2492del p.(Lys829IlefsTer7) variant destabilizes the structure of the Fn-III C7 domain, while the c.2663A > G p.(Asp888Gly) variant causes minimal structural alterations in the Ig C8 domain. Although the parents of the proband are heterozygous carriers for a single variant, they exhibit no musculoskeletal defects, suggesting a complex interplay between the two mutant alleles underlying this disorder. As emerging novel variants in MYBPC1 are shown to be causatively associated with musculoskeletal disease, it becomes clear that MYBPC1 should be included in relevant genetic screenings.
Subject(s)
Arthrogryposis , Muscular Diseases , Humans , Arthrogryposis/genetics , Arthrogryposis/metabolism , Mutation, MissenseABSTRACT
Desmoplakin (DSP) is a large (~260 kDa) protein found in the desmosome, the subcellular structure that links the intermediate filament network of one cell to its neighbor. A mutation "hot-spot" within the NH2-terminal of the DSP protein (residues 299-515) is associated with arrhythmogenic cardiomyopathy. In a subset of DSP variants, disease is linked to calpain hypersensitivity. Previous studies show that calpain hypersensitivity can be corrected in vitro through the addition of a bulky residue neighboring the cleavage site, suggesting that physically blocking calpain accessibility is a viable strategy to restore DSP levels. Here, we aim to find drug-like molecules that also block calpain-dependent degradation of DSP. To do this, we screened ~2500 small molecules to identify compounds that specifically rescue DSP protein levels in the presence of proteases. We find that several molecules, including sodium dodecyl sulfate, palmitoylethanolamide, GW0742, salirasib, eprosarten mesylate, and GSK1838705A prevent wildtype and disease-variant-carrying DSP protein degradation in the presence of both trypsin and calpain without altering protease function. Computational screenings did not predict which molecules would protect DSP, likely due to a lack of specific DSP-drug interactions. Molecular dynamic simulations of DSP-drug complexes suggest that some long hydrophobic molecules can bind in a shallow hydrophobic groove that runs alongside the protease cleavage site. Identification of these compounds lays the groundwork for pharmacological treatment for individuals harboring these hypersensitive DSP variants.
ABSTRACT
Obscurins are giant cytoskeletal proteins with structural and regulatory roles. Obscurin-B (~870 kDa), the largest known isoform, contains 2 enzymatically active Ser/Thr kinase (kin) domains, kin1 and kin2, which belong to the myosin light chain kinase family. Kin1 binds to and phosphorylates N-cadherin, a major component of the intercalated disc, the unique sarcolemmal microdomain that mediates the mechanochemical coupling of adjacent cardiomyocytes. Obscurin-B containing kin1 and N-cadherin colocalize at cell junctions in embryonic rat ventricular myocytes (ERVMs), and their codistribution is regulated by Ca2+. Phosphoproteomics analysis revealed that obscurin-kin1 phosphorylates N-cadherin at Ser-788 located within the juxtamembrane region of its cytoplasmic domain, with an apparent Kcat of approximately 5.05 min-1. Overexpression of obscurin-kin1 or phosphomimic-Ser-788-Glu N-cadherin in ERVMs markedly increases cell adhesion and chemical coupling. Importantly, phosphomimic Ser-788-Glu N-cadherin exhibits significantly reduced binding to p120-catenin, while overexpression of phosphoablated Ser-788-Ala N-cadherin increases RhoA activity. Consistent with an essential role of the obscurin-kin1/N-cadherin axis in cardiomyocyte coupling, it is deregulated in end-stage human heart failure. Given the nearly ubiquitous expression of obscurin and N-cadherin, our findings may have broad applicability in deciphering the obscurin-kin1/N-cadherin axis that likely mediates cell coupling in diverse tissues and organs.
Subject(s)
Cadherins , Myocytes, Cardiac , Animals , Humans , Rats , Cadherins/metabolism , Muscle Proteins/metabolism , Myocytes, Cardiac/metabolism , Phosphorylation , Protein Isoforms/metabolismABSTRACT
PURPOSE: Oral anti-cancer agents (OAAs) represent a new frontier in cancer treatment, but we do not know how well patients incorporate the strategies that they are taught for managing the side effects of OAAs into their daily lives. The purpose of this study was to understand how OAA side effects influenced patients' lives and what strategies patients used to manage them. METHODS: The study used an interpretive descriptive design utilizing photo elicitation interviews (PEI). Two pharmacists employed at the study ambulatory oncology clinic assisted with recruitment. Participants took photos and subsequent interviews focused on talking to participants about each photo, eliciting participant perspectives describing side effects of OAAs and management strategies. A directed content analysis approach was used to analyze the transcribed interviews. RESULTS: A total of nine participants were included in the study. Three themes and associated sub-themes emerged: making changes to nutritional habits due to OAA side effects (hydration and food), strategies to alleviate OAA side effects (medication and non-medication related), and methods of coping with OAA effects (intra- and interpersonal). Changing nutritional habits was an important strategy to manage OAA side effects. Medication-related strategies to alleviate OAA side effects could be nuanced and, additionally, there was wide variability in coping methods used. CONCLUSION: Patient education on OAAs and side effects is not always tailored to each unique patient and their circumstances. This study uncovered how participants devised their own distinct strategies to prevent or manage OAA side effects in an effort to help improve patients' experiences when taking OAAs.
Subject(s)
Antineoplastic Agents , Drug-Related Side Effects and Adverse Reactions , Humans , Pilot Projects , Adaptation, Psychological , Ambulatory Care Facilities , Patient Outcome AssessmentABSTRACT
Background: While adverse events and toxicities related to cancer drug therapy in the ambulatory oncology setting are common and often rooted in communication challenges, few studies have examined the problems of communication or tested tools to improve communication in this unique, high-risk setting. Objective: To determine the feasibility and acceptability of a virtual interdisciplinary communication Workshop designed to strengthen communication across ambulatory oncology teams members. Methods: Surveys of patients and clinicians in one ambulatory oncology clinic were analyzed and informed the communication intervention: an interdisciplinary virtual Workshop. Workshop evaluation included an implementation survey measure and a structured debrief with Workshop attendees. Results: 87 patients and 56 clinicians participated in pre-workshop surveys that revealed patient satisfaction with timely care and information, yet a range of rating communication experiences with the clinical team, and clinicians perceiving a high amount of organizational safety, yet rated discussion of alternatives to normal work processes low. Survey results guided reflection and discussion within the Workshop. Six clinicians participated in the interactive Workshop. Feasibility and acceptability of the virtual Workshop were supported by formative and summative data, along with suggestions for improvement. Conclusions: The patient and clinician surveys coupled with an interactive virtual Workshop were feasible and acceptable. Implications for Practice: The Workshop identified opportunities for individual- and system-level improvements in clinical team communication. This promising strategy requires replication in larger, diverse practice samples. Foundational: Clinicians accepted an interactive workshop that incorporated clinic-specific data and communication strategies. The program is feasible and acceptable in ambulatory oncology settings.
ABSTRACT
Reliable models of renal failure in large animals are critical to the successful translation of the next generation of renal replacement therapies (RRT) into humans. While models exist for the induction of renal failure, none are optimized for the implantation of devices to the retroperitoneal vasculature. We successfully piloted an embolization-to-implantation protocol enabling the first implant of a silicon nanopore membrane hemodialyzer (SNMHD) in a swine renal failure model. Renal arterial embolization is a non-invasive approach to near-total nephrectomy that preserves retroperitoneal anatomy for device implants. Silicon nanopore membranes (SNM) are efficient blood-compatible membranes that enable novel approaches to RRT. Yucatan minipigs underwent staged bilateral renal arterial embolization to induce renal failure, managed by intermittent hemodialysis. A small-scale arteriovenous SNMHD prototype was implanted into the retroperitoneum. Dialysate catheters were tunneled externally for connection to a dialysate recirculation pump. SNMHD clearance was determined by intermittent sampling of recirculating dialysate. Creatinine and urea clearance through the SNMHD were 76-105 mL/min/m2 and 140-165 mL/min/m2, respectively, without albumin leakage. Normalized creatinine and urea clearance measured in the SNMHD may translate to a fully implantable clinical-scale device. This pilot study establishes a path toward therapeutic testing of the clinical-scale SNMHD and other implantable RRT devices.
Subject(s)
Kidneys, Artificial , Renal Insufficiency , Humans , Swine , Animals , Creatinine , Pilot Projects , Silicon , Swine, Miniature , Dialysis Solutions , UreaABSTRACT
The shift of funding organizations to prioritize interdisciplinary work points to the need for workflow models that better accommodate interdisciplinary studies. Most scientists are trained in a specific field and are often unaware of the kind of insights that other disciplines could contribute to solving various problems. In this paper, we present a perspective on how we developed an experimental pipeline between a microscopy and image analysis/bioengineering lab. Specifically, we connected microscopy observations about a putative mechanosensing protein, obscurin, to image analysis techniques that quantify cell changes. While the individual methods used are well established (fluorescence microscopy; ImageJ WEKA and mTrack2 programs; MATLAB), there are no existing best practices for how to integrate these techniques into a cohesive, interdisciplinary narrative. Here, we describe a broadly applicable workflow of how microscopists can more easily quantify cell properties (e.g., perimeter, velocity) from microscopy videos of eukaryotic (MDCK) adherent cells. Additionally, we give examples of how these foundational measurements can create more complex, customizable cell mechanics tools and models.
Subject(s)
Image Processing, Computer-Assisted , Animals , Image Processing, Computer-Assisted/methods , Microscopy, FluorescenceABSTRACT
PURPOSE: To describe policy and system-level interventions with potential to improve cancer care at six sites. METHODS: In 2016, six institutions received foundation support to develop unique multi-component interventions aimed at improving cancer care for underserved populations. These organizations, located across the United States, participated in a cross-site evaluation to assess the overall initiative impact and to identify potentially promising policy and system-level solutions for dissemination and broader implementation. A health system and policy tracking tool was developed to collect data from each site and included a description of their efforts, strategies employed, and changes achieved (e.g., new policies, clinical protocols). Tracking tool data were analyzed using rapid qualitative analyses and a matrix approach. Semi-structured interviews were conducted with site leaders (N = 65) and were analyzed by thematic analysis. RESULTS: Sites reported 20 system and policy efforts, which resulted in improvements to electronic health records and telehealth strategies, changes to hospital/health system policies, and standardized clinical protocols/guidelines, among others. Efforts were aimed at: (1) coordinating care across multiple providers, supported by patient navigators; (2) expanding psychosocial and supportive care; (3) improving patient-provider communication; and (4) addressing barriers to accessing care. Interview analyses provided insights into successful strategies, challenges, and implications of the COVID-19 pandemic on cancer care. CONCLUSIONS AND IMPLICATIONS FOR CANCER SURVIVORS: Despite advances in diagnosis and treatment, cancer care remains inequitable. System-level improvements aimed at eliminating common barriers faced by underserved populations offer opportunities to improve the delivery of equitable, effective, and efficient care.
ABSTRACT
The definitive treatment for end-stage renal disease is kidney transplantation, which remains limited by organ availability and post-transplant complications. Alternatively, an implantable bioartificial kidney could address both problems while enhancing the quality and length of patient life. An implantable bioartificial kidney requires a bioreactor containing renal cells to replicate key native cell functions, such as water and solute reabsorption, and metabolic and endocrinologic functions. Here, we report a proof-of-concept implantable bioreactor containing silicon nanopore membranes to offer a level of immunoprotection to human renal epithelial cells. After implantation into pigs without systemic anticoagulation or immunosuppression therapy for 7 days, we show that cells maintain >90% viability and functionality, with normal or elevated transporter gene expression and vitamin D activation. Despite implantation into a xenograft model, we find that cells exhibit minimal damage, and recipient cytokine levels are not suggestive of hyperacute rejection. These initial data confirm the potential feasibility of an implantable bioreactor for renal cell therapy utilizing silicon nanopore membranes.
Subject(s)
Nanopores , Silicon , Humans , Animals , Swine , Feasibility Studies , Kidney , Bioreactors , Cell- and Tissue-Based Therapy , Epithelial CellsABSTRACT
The intercalated disk is a cardiac specific structure composed of three main protein complexes-adherens junctions, desmosomes, and gap junctions-that work in concert to provide mechanical stability and electrical synchronization to the heart. Each substructure is regulated through a variety of mechanisms including proteolysis. Calpain proteases, a class of cysteine proteases dependent on calcium for activation, have recently emerged as important regulators of individual intercalated disk components. In this review, we will examine how calcium homeostasis regulates normal calpain function. We will also explore how calpains modulate gap junctions, desmosomes, and adherens junctions activity by targeting specific proteins, and describe the molecular mechanisms of how calpain dysregulation leads to structural and signaling defects within the heart. We will then examine how changes in calpain activity affects cardiomyocytes, and how such changes underlie various heart diseases.
Subject(s)
Calcium , Calpain , Calpain/metabolism , Calcium/metabolism , Myocardium/metabolism , Myocytes, Cardiac/metabolism , Adherens Junctions/metabolismABSTRACT
Clinical islet transplantation for treatment of type 1 diabetes (T1D) is limited by the shortage of pancreas donors and need for lifelong immunosuppressive therapy. A convection-driven intravascular bioartificial pancreas (iBAP) based on highly permeable, yet immunologically protective, silicon nanopore membranes (SNM) holds promise to sustain islet function without the need for immunosuppressants. Here, we investigate short-term functionality of encapsulated human islets in an iBAP prototype. Using the finite element method (FEM), we calculated predicted oxygen profiles within islet scaffolds at normalized perifusion rates of 14-200 nl/min/IEQ. The modeling showed the need for minimum in vitro and in vivo islet perifusion rates of 28 and 100 nl/min/IEQ, respectively to support metabolic insulin production requirements in the iBAP. In vitro glucose-stimulated insulin secretion (GSIS) profiles revealed a first-phase response time of <15 min and comparable insulin production rates to standard perifusion systems (~10 pg/min/IEQ) for perifusion rates of 100-200 nl/min/IEQ. An intravenous glucose tolerance test (IVGTT), performed at a perifusion rate of 100-170 nl/min/IEQ in a non-diabetic pig, demonstrated a clinically relevant C-peptide production rate (1.0-2.8 pg/min/IEQ) with a response time of <5 min.
ABSTRACT
The study of rare or cryptic species in zoos can provide insights into natural history and behavior that would be difficult to obtain in the field. Such information can then be used to refine population assessment protocols and conservation management. The Bermuda skink (Plestiodon longirostris) is an endemic Critically Endangered lizard. Chester Zoo's successful conservation breeding program is working to safeguard, increase and reinforce skink populations in the wild. A key aim of this program is to develop our understanding of the behavior of this species. In this study, using 24 h video recordings, we examined the daily activity patterns, basking behavior and food preferences of four pairs of Bermuda skinks. The skinks displayed a bimodal pattern of activity and basking, which may have evolved to avoid the strength of the midday sun in exposed habitats in Bermuda. Captive Bermuda skinks appear to prefer a fruit-based diet to orthopteran prey. We also documented their reproductive behavior and compared it against two closely related species. Although there were many similarities between the courtship and mating behaviors of the three species, there was a significantly shorter period of cloacal contact in the Bermuda skink. Oophagia was also documented for the first time in this species. This knowledge has enabled the evaluation of the current ex-situ management practices of this species, filled gaps in knowledge that would be challenging to obtain in the field, and enabled the enhancement of both animal husbandry and reproductive success for the conservation breeding program.
Subject(s)
Endangered Species , Lizards , Animals , Conservation of Natural Resources/methods , Bermuda , Animals, Zoo , Plant BreedingABSTRACT
The N-terminal half of the giant cytoskeletal protein obscurin is comprised of more than 50 Ig-like domains, arranged in tandem. Domains 18-51 are connected to each other through short 5-residue linkers, and this arrangement has been previously shown to form a semi-flexible rod in solution. Domains 1-18 generally have slightly longer ~7 residue interdomain linkers, and the multidomain structure and motion conferred by this kind of linker is understudied. Here, we use NMR, SAXS, and MD to show that these longer linkers are associated with significantly more domain/domain flexibility, with the resulting multidomain structure being moderately compact. Further examination of the relationship between interdomain flexibility and linker length shows there is a 5 residue "sweet spot" linker length that results in dual-domain systems being extended, and conversely that both longer or shorter linkers result in a less extended structure. This detailed knowledge of the obscurin N terminus structure and flexibility allowed for mathematical modeling of domains 1-18, which suggests that this region likely forms tangles if left alone in solution. Given how infrequently protein tangles occur in nature, and given the pathological outcomes that occur when tangles do arise, our data suggest that obscurin is likely either significantly scaffolded or else externally extended in the cell.
Subject(s)
X-Ray Diffraction , Scattering, Small Angle , Magnetic Resonance SpectroscopyABSTRACT
BACKGROUND: During the COVID-19 pandemic, new intensive care units (ICUs) were created and clinicians were assigned or volunteered to work in these ICUs. These new ICU teams were newly formed and may have had varying practice styles which could affect team dynamics. The purpose of our qualitative descriptive study was to explore clinician perceptions of team dynamics in this newly formed ICU and specifically understand the challenges and potential improvements in this environment to guide future planning and preparedness in ICUs. METHODS: We conducted 14 semistructured one-on-one interviews with six nurses and eight physicians from a newly formed 36- to 50-bed medical ICU designed for COVID-19 patients in a teaching hospital. We purposively sampled and recruited ICU nurses, medical/surgical nurses, fellows, and attending physicians (with pulmonary/critical care and anaesthesia training) to participate. Participants were asked about team dynamics in the ICU, its challenges, and potential solutions. We then used a rapid analytic approach by first deductively categorising interview data into themes, based on our interview guide, to create a unique data summary for each interview. Then, these data were transferred to a matrix to compare data across all interviews and inductively analysed these data to provide deeper insights into team dynamics in ICUs. RESULTS: We identified two themes that impacted team dynamics positively (facilitator) and negatively (barrier): interpersonal factors (individual character traits and interactions among clinicians) and structural factors (unit-level factors affecting workflow, organisation, and administration). Clinicians had several suggestions to improve team dynamics (e.g., scheduling to ensure clinicians familiar with one another worked together, standardisation of care processes across teams, and disciplines). CONCLUSIONS: In a newly formed COVID ICU, interpersonal factors and structural factors impacted the team's ability to work together. Considering team dynamics during ICU reorganisation is crucial and requires thoughtful attention to interpersonal and structural factors.