Stéphane Larochelle

Genomics: CRISPR–Cas goes RNA

CasRx is a programmable CRISPR–Cas system that targets RNA for efficient knockdown and splicing modulation.

Proteomics: Bottoms-up!

Developments in data-independent-acquisition mass spectrometry allow efficient and accurate quantitation of peptidoforms across large sample cohorts.

Proteomics: The proof of splicing is in the proteome

An integrated workflow allows the quantitative interrogation of the impact of alternative splicing at the proteome level.

Systems biology: Protein isoforms: more than meets the eye

Alternative splicing imparts distinct functions through isoform-specific protein– protein interactions. The alternative splicing of transcripts is known to contribute to the diversity of the proteome by allowing single genes to produce several distinct protein isoforms. In some extreme cases the functions of two isoforms of the same protein can have opposing effects on a cellular process (cell survival versus death, for example), but most translated splice variants are thought to function in closely related biochemical pathways. To get a better handle on the functional consequences of alternative splicing on a global scale, Marc Vidal of Harvard University, Yu Xia of McGill University, and Lilia Iakoucheva of the University of California, San Diego, led an effort to systematically compare differences in protein–protein interactions for splice-variant isoforms of several hundred human genes. SYSTEMS BIOLOGY

Nanotechnology: Lock-and-key PORE-igami

A nanopore built from DNA allows the controlled and selective transport of organic molecules across a lipid membrane.

Proteomics: Tracking the proteome

A combination of quantitative mass spectrometry, subcellular fractionation and stringent statistical analyses allows the description of protein translocation events at the proteome scale.

Proteomics: A pluripotent approach

A combination of protein and DNA isolation methods expands our grasp of cellular reprogramming.

Imaging: RNA catch and release

The binding of single RNA molecules to individual proteins can be observed in the subcellular compartments of living cells.

Proteomics: STOMPing at the bits

In STOMP, a fixed specimen is first stained with antibodies or fluorescent dyes to identify regions containing deposits. These areas are recorded as a digital mask file, and laser illumination is used to cross-link a six-histidine-conjugated photo-affinity tag in an automated fashion. Two-photon microscopy allows for a cross-linking volume smaller than 1 μm3, enabling covalent attachment of the phototag to the target region with high precision. The sample is solubilized and the tagged proteins are purified by metal affinity prior to mass spectrometric identification. To demonstrate STOMP’s capabilities, Chakrabartty and colleagues analyzed the composition of amyloid plaques from an AD mouse model. As expected, the procedure identified a large amount of Aβ. In addition, 62 proteins were assigned a high probability of being associated with plaques, including SNAP25, VAMP2, synapsin 1 and ApoE, all PROTEOMICS

Structural biology: Solving XFEL's image problem

Improved XFEL crystallography data processing methods enable structure determination from limited samples.