News & Comment

Conrad Waddington famously used his epigenetic landscape to describe the paths a cell might take during developmental differentiation. In this analogy, the undifferentiated stem cell begins at the highest elevation and proceeds to tumble downward towards its final resting place, representing terminal differentiation. This general concept elegantly captures the essence of developmental transitions, but recent single-cell studies by Dr. Joanna Wysocka’s research group indicate that an alternative strategy underlies development of cranial neural crest cells. Published in Science, Antoine Zalc, Rahul Sinha and colleagues discovered that ectoderm-derived cranial neural crest cells undergo a developmental reprogramming event in vivo, expanding their differentiation potential through the reactivation of pluripotency, in effect rolling backwards up Waddington’s development landscape before eventually differentiating into mesenchymal lineages.

Willias Masocha is a Professor in the Department of Pharmacology & Therapeutics at Kuwait University where he studies the pathophysiology and treatment of neuropathic pain. Professor Masocha obtained a Bachelor of Pharmacy Honours from the University of Zimbabwe followed by a PhD in Pharmacology at the University of Granada before undertaking his postdoctoral training and International Brain Research Organization (IBRO) fellowship at the Karolinska Institutet. He began his independent research career at Kuwait University in 2006. In this Q&A he tells us about his current work and his perspectives on neuroscience research in the Middle East and Africa. He also shares tips for young scientists—particularly those based in Africa.

A recent meeting at Cold Spring Harbor Laboratory focused on emerging nucleic acid therapies and the essential academic research that has enabled them. The program encompassed everything from chemical innovations to preclinical and clinical progress, and provided a glimpse of the breakthroughs yet to come.

Recent advances in sequencing and barcoding technologies have enabled researchers to simultaneously profile gene expression, chromatin accessibility, and/or protein levels in single cells. However, these multiomic techniques often pose technical and financial barriers that limit their practicality. Kevin Wu and colleagues recently developed BABEL, a deep learning algorithm that can effectively translate between transcriptomic and chromatin profiles in single cells, thereby enabling researchers to perform multiomic analyses from an individual dataset.

Leila Akkari began her independent career in 2017 as an Assistant Professor at the Netherlands Cancer Institute in Amsterdam after working at Memorial Sloan Kettering Cancer Center in NYC. Two years ago, she was selected as one of the junior members of the Oncode Institute, a virtual group of cancer research labs based on the Netherlands. In this short Q&A, she tells us about her research and how her diverse background has helped her as a scientist. Dr. Akkari also shares some great pointers on the biggest hurdles women in STEM face and tips to overcome them.

The progressive loss of CD4 + T cells has been recognised as being central to HIV-1 pathogenesis, however a precise understanding of the underlying mechanisms and, consequently, improved therapies have yet to be achieved. Zhang et al. have recently shown in HIV-1 patients that the NLRP3 inflammasome pathway, which plays a key role in innate immunity, is a crucial mediator of the loss of CD4 + T cells. This advance could inform the development of innovative anti-HIV-1 therapies.

Climate change has been shown to affect the interannual variation and synchrony among individuals in seed production of masting trees, yet the proximate mechanisms driving these patterns remain unclear. A recent study by Michał Bogdziewicz and colleagues shows that the relationship between weather cues and seed initiation weakens in European beech as warming increases, resulting in progressive asynchrony of seed maturation. This study emphasizes the vulnerability of the relationship between environmental cues and forest reproduction to climate change.

Sepsis-associated encephalopathy, as well as increasing mortality, has been associated with long-lasting depressive behaviour, which is thought to be caused by infection-induced neuroinflammation in the brain. Saito et al. have recently demonstrated in a mouse model of sepsis that infiltrated regulatory T cells in the cerebral cortex mediate the resolution of neuroinflammation and alleviate anxious/depressive behaviour. Their study paves the way for further research that investigates the role of T cells in the underlying mechanisms mediating recovery of sepsis-associated depression.

A new year symbolizes new hope for the future, especially this year as we start to see the first wave of vaccines administered against COVID-19. Here, we take stock of the year behind us and look forward to seeing where science takes us in 2021.

While loss-of-function mutations affecting the α2-Na/K ATPase are known to cause familial hemiplegic migraine, it is unclear how reduced protein activity could contribute toward migraine or paralysis observed in patients. A recent study from Sarah Smith and colleagues demonstrates that conditional deletion of the α2-Na/K ATPase in astrocytes can evoke episodic paralysis in mice, potentially due to altered metabolic processing of serine and glycine. By feeding juvenile α2-Na/K ATPase mutant mice a serine- and glycine-free diet, the authors are able to prevent the onset of episodic paralysis. This study suggests that loss of α2-Na/K ATPase in astrocytes may affect amino acid metabolism in the brain, ultimately leading to episodic paralysis.

A huge amount of intrigue surrounds the aging process. Senescence—the decreased likelihood of reproduction and the increased chance of mortality—is a hallmark of aging. The reduced ability of senescent cells to maintain protein homeostasis (proteostasis) has been well-established in nematodes but this phenomenon had yet to be directly demonstrated in human cells. Sabath et al. recently provided compelling evidence that proteostasis collapse is indeed intrinsic to human cell senescence, which may have broad implications in the underlying processes of human aging.

Lorin Crawford began his independent career at Brown University School of Public Health with his own lab in the summer of 2017. He is currently a Senior Researcher at Microsoft Research, New England while also keeping his faculty position at Brown University. In this short Q&A he tells us about his research and the effect the pandemic has had on his lab and science. Dr. Crawford also shares some great tips on academic careers and making biostatistics approachable to wider audience and his views on the most exciting application of machine learning.

Protein aggregation and phase separation appear to play important roles in diseases like amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia (FTLD), but the interplay between different participating molecular events-which may facilitate or inhibit one another-can be difficult to study by conventional ensemble methods. In a recent study, Kevin Rhine and co-workers make use of point mutations to demonstrate the contrasting behaviour of condensates arising from Glycine and Arginine FUS mutants using single molecules fluorescence measurements.