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.

Rui Wang et al. report a comprehensive analysis of nearly 13,000 SARS-CoV-2 genome sequences isolated from patients in the United States, comprising more than 7000 single mutations. They show that SARS-CoV-2 genomes cluster into four distinct groups and that two of these groups are potentially more infectious, underlining the urgent need for viral control strategies in the US.

Photoreceptor death is central to vision loss in various retinal diseases. Disruption of nutrient availability and cell metabolism may underlie photoreceptor death. In this review, Pan et al. focus on the recent advances in the understanding of photoreceptor metabolism and suggest novel targets for neuroprotective strategies that prevent blindness.

Ronquist, Kudlicka, Senderov and colleagues present universal probabilistic programming as a powerful method for modeling and inference in statistical phylogenetics. They provide an accessible introduction to these techniques and apply them in inferring complex patterns of diversification and turnover in birds.

Ghosh et al. show that a lens protein βA1-crystallin inhibits PTP1B activity, regulating the metabolism of retinal astrocytes. They find that knockdown of βA1-crystallin exacerbates the streptozotocin-induced diabetic retinopathy-like phenotype in mice, suggesting the possibility that the interaction between βA1-PTP1B may be targeted for diabetic retinopathy.

Gontu et al. conducted a longitudinal study in COVID patients in which they assessed the response trajectories of antibodies directed to the SARS-CoV-2 surface spike glycoprotein and in vitro SARS-CoV-2 live virus neutralizing titers. Their measurements demonstrate the presence of an optimum window for convalescent plasma donation as well as predictions of the most suitable donor type.

Tashiro et al. describe a new channelrhodopsin variant from a terrestrial algal species and the role of the C-terminal domain in regulatory function. This far-blue-shifted channelrhodopsin may contribute to optogenetic tool research in the future.

Shrestha et al. show that enhancing the sampling using Hamiltonian replica exchange molecular simulation (HREMD) leads to accurate unbiased ensembles of intrinsically disordered proteins. They find that standard molecular simulation cannot reproduce small-angle scattering data as well as HREMD, highlighting the utility of the suggested approach.

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.