Cell Biology

The funding landscape for public engagement with science (PES) is highly dynamic. More research is needed to better track and understand the rapidly evolving funding landscape in PES. This paper shares insights from an ongoing mapping of the funding landscape and offers recommendations for new research to improve the resolution of such maps.

Compartmentalization by phase separation is an emerging principle for regulating transcription. While the compartmentalization mechanisms by which cells regulate genetic activities in response to specific environmental signals remain largely unclear, a recent study by Gao et al. suggests that hypoxia induces the formation of phase-separated condensates, which impacts metastasis-related transcription through chromatin organization.

Technical advances over the past two decades have enabled robust detection of cell-free DNA (cfDNA) in biological samples. Yet, higher clinical sensitivity is required to realize the full potential of liquid biopsies. This opinion article argues that to overcome current limitations, the abundance of informative cfDNA molecules – such as circulating tumor DNA (ctDNA) – collected in a sample needs to increase. To accomplish this, new methods to modulate the biological processes that govern cfDNA production, trafficking, and clearance in the body are needed, informed by a deeper understanding of cfDNA biology. Successful development of such methods could enable a major leap in the performance of liquid biopsies and vastly expand their utility across the spectrum of clinical care.

With advances in underlying technologies such as complex multicellular systems, synthetic materials, and bioengineering techniques, we can now generate in vitro miniaturized human tissues that recapitulate the organotypic features of normal or diseased tissues. Importantly, these 3D culture models have increasingly provided experimental access to diverse and complex tissues architectures and their morphogenic assembly in vitro. This review presents an analytical toolbox for biological researchers using 3D modeling technologies through which they can find a collation of currently available methods to phenotypically assess their 3D models in their normal state as well as their response to therapeutic or pathological agents.

Brain organoids are important 3D models for studying human brain development, disease, and evolution. To overcome some of the existing limitations that affect organoid quality, reproducibility, characteristics, and in vivo resemblance, current efforts are directed to improve their physiological relevance by exploring different, yet interconnected, routes. In this review, these approaches and their latest developments are discussed, including stem cell optimization, refining morphogen administration strategies, altering the extracellular matrix (ECM) niche, and manipulating tissue architecture to mimic in vivo brain morphogenesis. Additionally, strategies to increase cell diversity and enhance organoid maturation, such as establishing co-cultures, assembloids, and organoid in vivo xenotransplantation, are reviewed. We explore how these various factors can be tuned and intermingled and speculate on future avenues towards even more physiologically-advanced brain organoids.

Pyroptosis is a lytic, proinflammatory type of programmed cell death crucial for the immune response to pathogen infections and internal danger signals. Gasdermin D (GSDMD) acts as the pore-forming protein in pyroptosis following inflammasome activation. While recent research has improved our understanding of pyroptosis activation and execution, many aspects regarding the molecular mechanisms controlling inflammasome and GSDMD activation remain to be elucidated. A growing body of literature has shown that S-palmitoylation, a reversible post-translational modification (PTM) that attaches palmitate to cysteine residues, contributes to multi-layered regulation of pyroptosis. This review summarizes the emerging roles of S-palmitoylation in pyroptosis research with a focus on mechanisms that regulate NLRP3 inflammasome and GSDMD activation.

The centrosome duplicates only once per cell cycle such that, in preparation for mitosis, cells contain two centrosomes, allowing the formation of a bipolar spindle and segregation of chromosomes to the two daughter cells. Defects in centrosome numbers have long been recognized in human tumors and are postulated to be a driver of malignancy through chromosome instability. However, current work has revealed a multitude of phenotypes associated with amplified centrosomes beyond mitotic defects that may play a role in disease onset and progression, including cancer. This review focuses on the complexity of outcomes connected to centrosome abnormalities and the challenges that result from aberrant loss and gain of centrosome numbers. We discuss the tumor-promoting and inhibitory roles of amplified centrosomes, and propose that their impact on both physiology and disease is intrinsically linked to cellular context.

The selective removal of mitochondria by mitophagy proceeds via multiple mechanisms and is essential for human well-being. The PINK1/Parkin and NIX/BNIP3 pathways are strongly linked to mitochondrial dysfunction and hypoxia, respectively. Both are regulated by ubiquitylation and mitochondrial import. Recent studies have elucidated how the ubiquitin kinase PINK1 acts as a sensor of mitochondrial import stress through stable interaction with a mitochondrial import supercomplex. The stability of BNIP3 and NIX is regulated by the SCFFBXL4 ubiquitin ligase complex. Substrate recognition requires an adaptor molecule, PPTC7, whose availability is limited by mitochondrial import. Unravelling the functional implications of each mode of mitophagy remains a critical challenge. We propose that mitochondrial import stress prompts a switch between these two pathways.