Publication highlights

Researchers at the Crick are trying to understand what goes on inside neurons; one approach is to establish where and when genes are active within them. In a collaboration with Joshua Edel and Alex Ivanov at Imperial, they have used a minimally invasive “nanotweezer” to extract mRNA from precise locations within living neurons, using a localised electric field. The researchers can do this repeatedly without harming the cell, enabling us to track changes in gene expression over time and from different regions of the same neuron. This allows them to determine how neurons respond to their environment with more precision than previously possible.

Long DNA molecules form the basis of our lives, and these must be intricately packed into chromosomes to be passed on from one cell generation to the next.

Key to DNA compaction is a ring-shaped protein complex called condensin. How condensin achieves this miraculous task remained mysterious. A popular idea is that condensin extrudes DNA loops, much like threading pieces of string through the eye of a needle. However, chromosomal DNA exists in a form that is likely too bulky to slide through the eye. In search for an alternative mechanism, Crick researchers made pure condensin and examined how it engages with DNA in a test tube. This approach revealed the striking ability of condensin to sequentially entrap two DNA molecules that find each other by pure chance. The researchers even watched this process happen in front of their own eyes using a specialized microscope. Collaborators from Hokkaido University in turn found compelling evidence for the new capture mechanism inside chromosomes of living cells. Together, these results change our way of thinking about chromosomes: condensin stitches up pieces of DNA to weave the fabric of a chromosome.

Research from the Schaefer lab has found that mice can sense extremely fast and subtle changes in the structure of odours and use this to guide their behaviour. The findings alter the current view on how odours are processed in the mammalian brain.

This important paper showed very high levels of infection amongst healthcare workers in a local hospital. It has influenced government policy – asymptomatic healthcare workers are to be screened as per our recommendation (announced October 12th).

Cryo-EM has the potential to study any native conformation of a macromolecule. However, the sample preparation time is high, compared to the timescale of most protein interactions and conformational changes. In this paper, we established a robust method of time-resolved cryo-EM sample preparation. We produced high-quality samples for microscopy while speeding up the process of making them by several orders of magnitude. This allowed samples to be collected within 30ms of the initiation of a biochemical reaction, within the timeframe of many critically important and interesting processes. This enables a whole new class of experiments in structural biology research.

Animals engage actively with their environment, yet how active sampling strategies impact neural activity was unknown. We showed that mice adapt sniffing during learning in a way that enhances neuronal representation. Furthermore, this work resolves a long-standing conundrum that seemingly non-olfactory information is prominently represented in the OB: context influences sniffing, which in turn changes neural activity.

Neuroprosthetics and neuroscience research alike are limited by the bandwidth of neural recording. At the same time, ever-more powerful silicon-based technology is ubiquitous in our phones, tablets and computers. Here we showed that progress in neural recording can be coupled to this by fusing bundles of microwires to pixel array chips, lifting silicon technology to the third dimension for deep brain recording.