The Kavli Prize 2018

Chloromethane (CH3Cl) has been observed towards a low-mass protostar and comet 67P, making it the first organohalogen detected in space. The species was previously considered to be a biomarker, but the authors suggest viable alternative abiotic formation routes.

The first extraterrestrial detections of a member of the organohalogen family of molecules have been made towards comet Churyumov–Gerasimenko and low-mass protostar IRAS 16293-2422. Chloromethane, considered to be a biomarker, can form efficiently abiotically.

The efficiency of the chemical desorption caused by the reactions between H₂S, HS and H on an icy grain surface analogue has been quantified by means of in situ infrared measurements of the surface, providing valuable information for understanding non-thermal desorption processes.

ALMA observations of TW Hydrae in the 13C18O J = 3–2 molecular line probe the mid-plane of the circumstellar disk where giant planets are expected to form. With other lines, the gas mass distribution, temperature and the gas-to-dust ratio are determined.

Giant planets like Jupiter need a large reservoir of gas to grow to full size. New observations indicate that such planetary nurseries last twice as long as previously thought.

In combination with existing observations and detailed circumstellar models, the detection of hydrogen deuteride emission from the star TW Hydrae implies a circumstellar disk mass of more than 0.05 solar masses, which is enough to form a planetary system like our own.

In situ measurement of O₂ in the coma of comet 67P/Churyumov–Gerasimenko shows local abundances ranging from one per cent to ten per cent relative to H₂O; the spatial and temporal uniformity of the O₂/H₂O ratio suggests that primordial O₂ was incorporated into the nucleus during the comet’s formation.

Our inventory of the molecular universe is continually progressing. Our understanding of the astrochemistry behind it will flourish if we are mindful of funding experimental and theoretical efforts as well as observational.

The detection of complex cyanides in the protoplanetary disk around the young star MWC 480, and the similarity of their abundance ratios to those found in comets, implies that the rich organic chemistry of our solar nebula was not unique.

Organic compounds called nitriles have been detected in material surrounding a young star. The finding hints at a vast reservoir of ice and volatile species that can seed the surfaces of young rocky planets or moons. See Letter p.198

In interstellar clouds, reactions that have an activation barrier have previously been considered too slow to be significant because of the low temperatures experienced. However, large enhancements in the rate coefficient for the reaction of OH with methanol have now been observed at temperatures below 100 K. A mechanism involving tunnelling has been proposed.

Chemical reactions with activation barriers generally slow to a halt in the extreme cold of dense interstellar clouds. Low-temperature experiments on the reaction of OH with methanol have now shown that below 200 K there is a major acceleration in the rate that can only be explained by enhanced quantum mechanical tunnelling through the barrier.

The solar wind, cometary ices, and inner Solar System bodies exhibit distinct nitrogen isotopic compositions. A synthesis of these analyses suggests that these distinct reservoirs may be the result of early fractionation processes.

Analysis of the N₂H⁺ — and, by inference, the N₂ — abundance inside a cold dark molecular cloud finds that most of the nitrogen is atomic, rather than molecular, explaining the low N₂ abundance in comets.

The rotational state of a molecule is not generally considered to play a role in how fast it reacts; however, when the temperature is low quantum effects become more important. Now, it is shown that at low temperatures rotationally excited H₂ molecules react with He faster than non-rotating ground-state molecules — a process mediated by stronger long-range attraction.

Observations of the outflow associated with the TMC1A protostellar system reveal that the ‘disk wind’ model correctly explains how material is ejected from protostars.

CRISPR is a microbial RNA-based immune system protecting against viral and plasmid invasions. The CRISPR system is thought to rely on cleavage of a precursor RNA transcript by Cas endonucleases, but not all species possessing CRISPR-type immunity encode Cas proteins. This study now describes an alternative pathway in Streptococcus pyogenes that employs trans-encoded small RNA that directs the processing of precursor RNA into crRNAs through endogenous RNase III and the CRISPR-associated Csn1 protein.

A new engineered version of SpCas9, called HypaCas9, displays enhanced accuracy of editing without significant loss of efficiency at the desired target.

Age-dependent epigenetic changes that are influenced by genetic factors contribute to lactase nonpersistence, which is linked to the inability of adult mammals to digest lactose.

CRISPR RNA-guided endonuclease Cas9 recognizes and cleaves the double-stranded DNA complementary to the RNA guide. Here the authors use high-speed atomic force micropcopy (HS-AFM) to visualize the conformational dynamics of Cas9 during its DNA targeting and cleavage processes.

Physical mapping of DNA can be used to detect structural variants and for whole-genome haplotype assembly. Here, the authors use CRISPR-Cas9 and high-speed atomic force microscopy to ‘nanomap’ single molecules of DNA.

Nature Biotechnology asks selected members of the international community to comment on the ethical issues raised by the prospect of CRISPR-Cas9 engineering of the human germline.

A fluorescence-based approach defines new features of Cas9 that control the specificity of RNA-guided DNA cleavage in CRISPR genome editing technology.

Gene editing in the mouse brain is achieved by injection of Cas9 ribonucleoprotein complexes.

The genome of human cells is edited using the bacterial RNA-guided Cas9 endonuclease.

The use of CRISPR–Cas technology for gene editing has rapidly become widespread. Here, Corn and colleagues discuss the applications of this revolutionary tool in drug discovery and development, describing how it could make substantial contributions to target identification and validation, animal models and cell-based therapies.

The unique capabilities of CRISPR technologies have enabled a broad range of applications in biomedicine and agriculture.

CRISPR-Cas9 can be used to edit both single and multiple genes in postmitotic neurons in adult mice enabling rapid assessment of gene functions in the brain.

Off-targets identified by whole-genome sequencing of CRISPR-treated mouse embryos and their genetic parents are compared to predictions from GUIDE-seq and computational methods.

CROP-seq enables pooled CRISPR screens for complex transcriptome signatures by making gRNA expression detectable in single-cell RNA sequencing.

The authors present a CRISPR-library-based approach for highly efficient and precise genome-wide variant engineering. They examine the functional consequences of premature termination codons within all annotated essential genes in yeast.

Nir Hacohen, Bruce Walker, David Sabatini, Eric Lander and colleagues perform a CRISPR–Cas9-based screen for host factors that are required for HIV infection. They identify two known and three novel factors that are necessary for viral infection but that are not required for cell viability, making them potential targets for antiviral therapy.

Yilmaz et al. generate a genome-wide loss-of-function library using human haploid embryonic stem cells and define genes that are essential for cell survival, growth and pluripotency maintenance, as well as growth-restricting genes.

New approaches to create site-specific gene replacements and insertions in plants have been developed based on intron-targeting CRISPR/Cas9. These approaches efficiently generate replacements and insertions at the OsEPSPS gene in rice, resulting in glyphosate-resistant plants.

Analysis of the ExAC and 1000 Genomes data sets estimates the impact of inter-individual variation on the efficacy and safety of therapies based on CRISPR endonucleases.

Gold nanoparticles carrying Cas9 ribonucleoprotein and donor DNA, and complexed with endosomal disruptive polymers, correct the DNA mutation that causes Duchenne muscular dystrophy in mice, with minimal off-target effects.

Using an adeno-associated virus–mediated, direct in vivo CRISPR screen, the authors mapped a quantitative landscape of glioblastoma suppressors. Their study revealed gene combinations that functionally drive gliomagenesis from normal glia in native mouse brains. The authors further demonstrate that mutational background can differentially influence gene expression and chemotherapeutic resistance.

Owing to their programmable ability to cut specific nucleic acid sequences, CRISPR–Cas systems have been used for precise genome engineering. In this Review, the authors discuss the chemistry and molecular mechanisms of interference by single-effector CRISPR–Cas proteins.

Auditory hair cells contain mechanotransduction channels that are activated by sound. The authors show that Piezo2, a mechanotransduction channel important for touch perception, is expressed in auditory hair cells. Surprisingly, Piezo2 is not the mechanotransduction channel essential for auditory perception and is instead observed after damage to hair cells.

The sensitivity, frequency resolution and dynamic range of hearing depend upon the cochlear active process, a mechanical-amplification system within the cochlea. In this Review, Hudspeth summarizes evidence that these features result from the operation of hair cells near a dynamical instability, the Hopf bifurcation.

Inner ear hair cells detect sound through deflection of stereocilia that harbor mechanically-gated channels. Here the authors show that protein responsible for Usher syndrome, CIB2, interacts with these channels and is essential for their function and hearing in mice.

Marina Cavazzana-Calvo and colleagues report mutations in the gene encoding mitochondrial adenylate kinase 2 in reticular dysgenesis, the most severe form of inborn combined immunodeficiency, characterized by the absence of granulocytes and almost complete deficiency of lymphocytes in peripheral blood.

This review describes how the genetic causes of the many forms of human deafness have provided insight into the molecular mechanisms of auditory transduction. In combination with mouse models, these genetic studies have elucidated the mechanisms behind the formation and functioning of the hair bundle as a mechanical transducer.

Mechanically sensitive transducer channels are responsible for the detection of sound-induced hair cell vibrations. However, the location of these channels in the stereociliary bundle has been unclear. Using high-speed calcium imaging, this study demonstrates that there are no transduction channels in the tallest row of stereocilia in the mammalian cochlea. Instead, these channels are more likely to be present in the bottom stereociliary rows.

Cochlear hair cells detect sound vibrations and generate force to enhance auditory sensitivity and frequency selectivity. Fettiplace and Hackney describe proteins involved in the sensory and motor functions of outer hair cells, presenting evidence for two types of force production.