Cellular & Molecular Imaging

The cell cycle is canonically described as a series of four consecutive phases: G1, S, G2, and M. In single cells, the duration of each phase varies, but the quantitative laws that govern phase durations are not well understood. Using time-lapse microscopy, we found that each phase duration follows an Erlang distribution and is statistically independent from other phases. We challenged this observation by perturbing phase durations through oncogene activation, inhibition of DNA synthesis, reduced temperature, and DNA damage. Despite large changes in durations in cell populations, phase durations remained uncoupled in individual cells. These results suggested that the independence of phase durations may arise from a large number of molecular factors that each exerts a minor influence on the rate of cell-cycle progression. We tested this model by experimentally forcing phase coupling through inhibition of cyclin-dependent kinase 2 (CDK2) or overexpression of cyclin D. Our work provides an explanation for the historical observation that phase durations are both inherited and independent and suggests how cell cycle progression may be altered in disease states.

DNA-FISH and BRD4 immunofluorescence confocal stacks targeting PTC regions described in Klonizakis et al. 2023

This is source data for both: 1) EED IF Confocal Image data during 3 different synchronization time points; 2) RPB1-Dendra2 STORM raw data for 2 time points.

Loss of polarity is a hallmark of cancer, and the related epithelial-to-mesenchymal transition (EMT) phenotype also impacts prognosis and therapy outcomes, particularly in colorectal cancer (CRC). However, the mechanisms and drugs that impact these morphological changes are understudied, due to the complete failure of typical live/dead 2D high-throughput screens to capture morphology or the lack of robustness of 3D screens. We designed a high-throughput screen using 3D type I collagen cultures of CRC cells to assess morphological changes in colonies and identified several FDA-approved drugs that re-epithelialize CRC colonies (images uploaded here are images from screen). One of these drugs, azithromycin, increased colony circularity, enhanced E-cadherin membrane localization and ZO-1 localization to tight junctions, caused transcriptomic changes consistent with downregulation of epithelial-to-mesenchymal transition, and elevated sensitivity to the chemotherapeutic, irinotecan. A retrospective analysis of patient data demonstrated that the use of azithromycin in patients undergoing treatment for CRC with irinotecan had improved the 5-year survival compared to the chemotherapy alone. These results highlight the importance of morphological screens to identify novel drug candidates and synergistic mechanisms.

Polyphasic studies on cyanobacterial biodiversity are scarce in the Caribbean and have never been conducted in the Dominican Republic. In this study we analysed sixteen cyanobacterial isolates sampled from biofilms growing on rocks and related to freshwater, saline and thermal environments across the country. A polyphasic approach was employed, incorporating 16S rRNA gene phylogenetic analysis, molecular identity assessments (p-distance), 16S–23S ITS sequence comparison and secondary structure analysis, alongside morphological characterization and habitat comparison. The strains were distributed across the orders Nodosilineales, Oculatellales, Oscillatoriales and Nostocales. Eleven strains were identified as belonging to Almyronema, Euryhalinema, Salileptolyngbya, Nodosilinea, Reticulonema, Vacuolonema, Capilliphycus, Purpureonostoc, Violetonostoc, Desmonostoc and Hapalosiphon. Additionally, four strains formed three distinct clades and presented low 16S rRNA gene identities with their phylogenetically closest genera, suggesting the existence of three undescribed lineages pending comprehensive polyphasic study. At the species level, four strains were considered undescribed lineages pending comprehensive polyphasic study and one strain (LEGE 171504) was described as a new species of Salileptolyngbya. This study represents the first investigation into the cyanobacterial diversity of Dominican Republic expanding the distribution of the identified taxa. Moreover, this is the first report of Salileptolyngbya in the Caribbean region and in brackish waters, as well as the first newly described cyanobacterial species from the Dominican Republic.

Ultrasound imaging to assess the functionality of the heart and determine the presence of a mutant phenotype through echocardiographic measurements.

Aberrant biomolecular condensates are implicated in multiple incurable neurological disorders, including Amyotrophic Lateral Sclerosis, Frontotemporal Dementia, and DYT1 dystonia. However, the role of condensates in driving disease etiology remains incompletely understood. Here, we establish myeloid leukemia factor 2 (MLF2) as a disease-associated phase transition biomarker and develop a scalable high-content platform that identifies condensate modulators across broad chemical and genetic space. We uncover FDA-approved drugs that remodel aberrant condensate composition, validating the approach for drug discovery. A genome-wide CRISPR/Cas9 screen identifies genes linked to microcephaly and related neurodevelopmental disorders whose loss drives nuclear condensate accumulation. Machine learning resolves two phenotypic clusters: RNF26 deletion induces nuclear envelope condensates reminiscent of nuclear pore defects, whereas loss of microcephaly-associated ZNF335 drives accumulation of distinct nucleoplasmic condensates. Our study provides a scalable resource for identifying corrective modulators of aberrant condensates and establishes a link between dysregulated phase transitions and neurodevelopmental disorders.

The Darwin Tree of Life project has the goal to sequence the genomes of 70,000 species of eukaryotic organisms in Britain and Ireland. This is a collection of photographs of the samples included in the study, provided by the National History Museum (NHM).

"This dataset comprises processed images and class labels of UV microscopy images of human red blood cells infected with malaria at various degrees of parasitemia. The microscope used to caputure the images is a custom-built UV microscope employing a quartz Zeiss Ultrafluar 100x/0.85 finite conjugate objective. The cells are imaged at either one wavelength in deep UV (285 nm) or three simultaneous wavelengths (285 nm, 365 nm, 565 nm). Each condition contains many fields of view, extensive z-stacks, and a single time point. The directory structure is organized first by category: 'Training and validation', or 'Titration 2020-06-20'. Training and Validation is a collection of time-stamped data collection sessions acquired during development of the method. 'Titration 2020-06-20' is an experiment whereby a high parasitemia malaria culture was diluted serially into healthy red blood cells. Each dilution point was imaged and resides in a time-stamped directory."

Tara Expeditions are global scientific voyages that probe morphological and molecular diversity, evolution and ecology of marine plankton to explore how they are impacted by changes in the Earth's climate. The first expeditions collected samples of marine plankton containing viruses, bacteria, archaea, protists and planktonic metazoans living in the photic layer of the world's oceans. These expeditions, the first taking place between 2009 and 2013, include Tara Oceans: a global view, and Tara Oceans Polar Circle, both of which followed the same sampling protocol. This dataset includes 1074 pictures of 284 planktonic taxa (mainly microalgae and other Ciliate and Radiolarian protists) collected from the vicinity of the Marquesas Islands in the Southern Pacific Ocean during the Tara Oceans expedition. Multiple samples particularly of the size fractions 5-20 and 20 180 um from four sites and two depths were processed with different methods and studied in detail using scanning electron microscopy.