Highlighted papers
For a complete list of papers, take a look at Gautam’s Google Scholar or ORCID profiles.
We read, review and post preprints.
Lab Google scholar profiles: Jana Helsen | Hiral Shah
At EMBL
Reza H et al.
Expansion microscopy reveals unique ultrastructural features of pathogenic budding yeast species
bioRxiv, 2024 DOI: 10.1101/2024.02.20.581313
We establish ultrastructural expansion microscopy (U-ExM) in seven pathogenic yeasts including Candida albicans. Using protein pan-labelling and immunofluorescence of native and tagged proteins, we outline organelle dynamics through the cell cycle. U-ExM uncovers differences in SPB and spindle organisation and dynamics in C. albicans compared to model budding yeast S. cerevisiae.
Hashim was scientific visitor with the lab for three months learning and optimising U-ExM for a variety of yeasts.
We show that the number of kinetochore-microtubule attachment points at centromeres impose a constraint on chromosome number evolution. An insufficient number of attachments result in a force imbalance in the metaphase spindle, declustering kinetochores.
Our work provides an experimental example of how the mechanics of a core cellular process can constrain evolutionary processes.
This preprint is a result from the close collaboration between us and the lab of Gavin Sherlock.
Evolutionary cell biology explores the origins, principles, and core functions of cellular features and regulatory networks through the lens of evolution. This emerging field relies heavily on comparative experiments and genomic analyses that focus exclusively on extant diversity and historical events, providing limited opportunities for experimental validation. In this opinion article, we explore the potential for experimental laboratory evolution to augment the evolutionary cell biology toolbox, drawing inspiration from recent studies that combine laboratory evolution with cell biological assays. Primarily focusing on approaches for single cells, we provide a generalizable template for adapting experimental evolution protocols to provide fresh insight into long-standing questions in cell biology.
Remodelling of the nuclear envelope remodelling during cell division can be vastly different between eukaryotes. Some disassembling their envelope, some divide using an intranuclear spindle, but the evolutionary reasons for adopting one or the other are unclear. Here, we use an integrated comparative genomics and ultrastructural imaging approach to investigate mitotic strategies in Ichthyosporea, close relatives of animals and fungi. Species within this clade have diverged towards either a fungal-like closed or an animal-like open mitosis, most likely to support distinct multi- or uninucleated states. Our results suggest that multinucleated life cycles favour the evolution of closed mitosis.
This preprint emerged from a close collaboration between us and the labs of Omaya Dudin, Yannick Schwab, and Iva Tolić.
Here, by using mutant cells exhibiting altered attachment behaviours of mitochondria to microtubules, we show their important role in determining division symmetry. Changes in the attachment of Mts and mitochondria resulted in errors in nuclear positioning and asymmetric cell division.
To allow for a quantification of contact sites, we were happy to contribute U-ExM data for all three strains.
Here, we present an ultrastructure expansion microscopy (U-ExM) protocol optimised for use in the model yeasts S. cerevisiae and S. pombe. Increasing the sample size by a factor of roughly four allows for 3D super resolution on conventional microscopy systems. For this publication, we use it to investigate the spatial organisation of the spindle pole body (SPB) and count nuclear pore complexes (NPCs). Combining those specific labels with a general protein staining enables an investigation of subcellular structures within a cellular context.
A major additional improvement was presented by using high pressure freezing instead of chemical fixation methods to preserve structures in a near native state. This further enabled the detection of several proteins with specific antibodies that, in chemical fixations, did not yield sufficient signals - such as for tubulin.
In this review, we discuss the cellular properties and processes that contribute to nuclear size and shape control, drawing examples from across eukaryotes and highlighting conserved themes and pathways. We then outline physiological roles that have been uncovered for specific nuclear morphologies and disease pathologies associated with aberrant nuclear morphology.
Fraser N, Brierley L, Dey G, Polka JK, Pálfy M, Nanni F, Coates JA.
The evolving role of preprints in the dissemination of COVID-19 research and their impact on the science communication landscape.
PLoS Biol. 2021 Apr 2;19(4):e3000959. DOI: 10.1371/journal.pbio.3000959.
Over 125,000 COVID-19-related scientific articles were released within 10 months of the first confirmed case, of which more than 30,000 were hosted by preprint servers. We investigated the attributes of COVID-19 preprints, their access and usage rates, as well as characteristics of their propagation on online platforms. Our data provide evidence for increased scientific and public engagement with preprints related to COVID-19 (COVID-19 preprints are accessed more, cited more, and shared more on various online platforms than non-COVID-19 preprints), as well as changes in the use of preprints by journalists and policymakers. We also find evidence for changes in preprinting and publishing behaviour: COVID-19 preprints are shorter and reviewed faster.
All eukaryotic cells must partition the nuclear envelope in lockstep with cell division at the end of each cell cycle. Cells have evolved a wide range of strategies to carry out nuclear division. We discuss shared and divergent features of these mitotic strategies and speculate on their evolutionary origins.
Before EMBL
Dey G, Culley S, Curran S, et al.
Closed mitosis requires local disassembly of the nuclear envelope.
Nature. 2020 Sep;585(7823):119-123. DOI: 10.1038/s41586-020-2648-3.
We show that ‘closed’ mitosis in the fission yeast Schizosaccharomyces pombe occurs via local disassembly of the nuclear envelope within the narrow bridge connecting segregating daughter nuclei; we identify a key role for Les1 in this process, which restricts nuclear envelope breakdown to the bridge. We find that the regulatory logic of ‘local’ NEB mirrors that of NEB in open mitosis, hinting at the existence of universal NE remodelling mechanisms with implications for our understanding of eukaryotic evolution.
The hyperthermophilic archaeon Sulfolobus is a close relative of the first eukaryotes, and uses ESCRTIII to divide. We constructed the world’s first 75C microscope to image Sulfolobus cells dividing live.
Loss of gene function is common throughout evolution, even though it often leads to reduced fitness. Using experimental evolution of hundreds of budding yeast strains, we found that gene loss can be compensated and can ultimately even facilitate and enhance adaptation.
Newly discovered archaeal genomes encode homologs of key eukaryotic gene families, including cytoskeletal regulators and small GTPases. What does that mean for the cell biology of the archaeal ancestors of eukaryotes, and will these genomes shed light on the evolution of the first eukaryotes, over 2 billion years ago?
Dey G, Jaimovich A, Collins SR, Seki A, Meyer T.
Systematic Discovery of Human Gene Function and Principles of Modular Organization through Phylogenetic Profiling.
Cell Reports. 2015 Feb;10(6):993-1006. DOI: 10.1016/j.celrep.2015.01.025.
Genes that share an evolutionary history are likely to share molecular functions and cellular roles. We make use of this principle to identify co-evolving modules in the human genome, and help assign functions to uncharacterised human genes.
Dey G, Gupta GD, Ramalingam B, et al.
Exploiting cell-to-cell variability to detect cellular perturbations. Plos one. 2014 ;9(3):e90540. DOI: 10.1371/journal.pone.0090540.
Genome-wide functional screens can be incredibly powerful tools, but come with a unique set of challenges, including high levels of variability that can mask subtle results. We develop an algorithm to exploit the variability between cells to detect subtle perturbations in an RNAi screen for endocytosis.