Publication highlights

Go inside our research

Explore a selection of research case studies from the past five years.

Read now
A Crick researcher reading a scientific paper on a screen.

Researchers at the Crick are tackling the big questions about human health and disease, and new findings are published every week.

Our faculty have picked some of the most significant papers published by Crick scientists, all of which are freely available thanks to our open science policy.

Picture of a self-establishing community (SeMeCo), a yeast cell model used by researchers to study the exchange of metabolites between cells

New method to understand protein biomarkers in plasma

In recent years, the Ralser lab have developed new methods to understand proteins in plasma – the liquid part of the blood – with the hope of discovering new protein biomarkers, which are indicators for a wide range of diseases.

However, the structure and function of proteins is highly influenced by chemical modifications. One such modification – glycosylation – happens to lots of different proteins in plasma and is known to be altered in diseases such as cancer. Currently, methods to study protein glycosylation in plasma are relatively limited, generally requiring additional handling steps. The team developed a method capable of quantifying over a thousand glycopeptide features from human plasma without any extra steps, making it compatible to understanding data from large clinical trials.

They then applied this method to a cohort of COVID-19 patients and healthy donors, finding changes in glycosylation of plasma proteins in response to increasingly severe COVID-19. They hope this method can be applied for larger epidemiological and clinical studies, both to better understand the underlying biology and develop new biomarkers.

Oxonium ion scanning mass spectrometry for large-scale plasma glycoproteomics

Published in Nature Biomedical Engineering

Published

Young and old microbes work together to increase their lifespans

An international collaboration led by Crick Group Leader Marcus Ralser has shown that mixed communities of young and old yeast cells can co-operate and exchange resources, increasing the lifespan of all the cells. They focused on the processes used by cells to exchange metabolites, which are produced when cells create energy, and include amino acids. When young yeast cells released amino acids into the environment, these could be taken up by older cells, and the whole community of cells lived longer. One of the amino acids, methionine, was of particular importance as it is needed to kickstart the process of building proteins and is also important in many cellular processes. Uptake of methionine changed the metabolism of the older cells, affecting key anti-ageing pathways and also led to the release of metabolites with protective properties into the environment, which could then be taken up by other cells. If applicable to higher organisms, the concept underlying these results could add a new dimension to studying cells in health and disease.

Cell-cell metabolite exchange creates a pro-survival metabolic environment that extends lifespan

Read Crick news article

Published in Cell

Published

Protein signature identifies those at highest risk from severe infection

Chromosomes are formed from chromatin, a complex of DNA and proteins. When cells die, chromatin is released into the surroundings and can cause inflammation and cytotoxicity. A process known as chromatin clearance is needed to remove extracellular chromatin and protect against severe disease. A collaboration led by Crick group leader Veni Papayannopoulos has found that in samples taken from people with the severest form of COVID-19 pneumonia, chromatin clearance was hindered in all cases, and when this process was affected the most, patients were less likely to survive.

Further analysis of the chromatin buildup showed that DNAses, a group of enzymes that help to break down chromatin, were being inhibited by another molecule, actin, which is released when cells die. Blood plasma samples taken from a second group of patients with microbial sepsis demonstrated a build-up of chromatin which correlated with high levels of actin in the blood. Using this information, the team developed a ‘proteomic profile’, a signature of protein levels and enzyme activity in the blood, that characterised the most severe and high-risk cases of infection. With further development, this signature could be used to help distinguish patients who might require additional treatment.

Functional proteomic profiling links deficient DNA clearance with increased mortality in individuals with severe COVID-19 pneumonia

Read Crick news article

Published in Immunity

Published

A fight to the death between neutrophils and fungi

The mechanisms linking systemic infection to hyperinflammation and immune dysfunction in sepsis are poorly understood. Extracellular histones, which appear when cells die and free chromatin is released, promote sepsis pathology, but their source and mechanism of action were unclear. Researchers in the Papayannopoulos lab have shown that myeloperoxidase, released from neutrophils, can suppress histone release, but ongoing fungal colonisation of the spleen eventually triggers T cell death, which releases free chromatin, and hence, histones. This induces cytokines, including G-CSF, that reduce the lifespan of mature neutrophils, thereby depleting the protective population. The pathway is relevant to the clinic, as deaths from sepsis are associated with high levels of neutrophil lifespan-shortening activity.

Microbe capture by splenic macrophages triggers sepsis via T cell-death-dependent neutrophil lifespan shortening

Published in Nature Communications

Published

Give and take in the exometabolome

Microbial communities are composed of cells of varying metabolic capacity, and regularly include auxotrophs that lack essential metabolic pathways, whose usefulness to the community is therefore puzzling. A study from the Ralser lab revealed that metabolic changes in auxotrophs enrich the microbial community exometabolome—the mixture of secreted extracellular metabolites—and increase drug resistance. The findings could help the development of more effective antimicrobial treatments.

Microbial communities form rich extracellular metabolomes that foster metabolic interactions and promote drug tolerance

Read Crick news article

Published in Nature Microbiology

Published

DIA-NN: neural networks and interference correction enable deep proteome coverage in high throughput

This paper demonstrates the power of neural networks in deconvoluting complex biological data. We developed an easy-to-use integrated software suite, DIA-NN, that exploits deep neural networks and new quantification and signal correction strategies for the processing of data-independent acquisition (DIA) proteomics experiments. DIA-NN improves the identification and quantification performance in conventional DIA proteomic applications, and is particularly beneficial for high-throughput applications, as it is fast and enables deep and confident proteome coverage when used in combination with fast chromatographic methods.

View the publication

Published in Nature Methods

Published

Lysine harvesting is an antioxidant strategy and triggers underground polyamine metabolism

We report a new and powerful metabolic anti-stress mechanism, ‘Lysine harvesting’, that protects microbial cells in stress situations. We noticed that extracellular lysine is taken up to reach concentrations up to 100x higher than those required for growth. Uptake is dependent on the polyamine pathway, connected via promiscuous metabolic reactions, and triggers a reprogramming of redox metabolism: NADPH is channelled into glutathione metabolism, leading to a large increase in glutathione, lower levels of reactive oxygen species and increased oxidant tolerance. Therefore, nutrient uptake occurs not only to enable cell growth, but allows cells to reconfigure their metabolism to preventatively mount stress protection.

View the publication

Published in Nature

Published

A COVID-19 virus particle

Ultra-high-throughput clinical proteomics reveals classifiers of COVID-19 infection

Point-of-care diagnostic classifiers for COVID-19 are urgently required. Here, we present a platform for ultra-high-throughput serum and plasma proteomics that can be implemented in regulated clinical laboratories. We use our platform to identify 27 potential biomarkers that are differentially expressed depending on the WHO severity grade of COVID-19. They include complement factors, the coagulation system, inflammation modulators, and pro-inflammatory factors upstream and downstream of interleukin 6. All protocols and software for implementing our approach are freely available. This work supports the development of routine proteomic assays to aid clinical decision making and generate hypotheses about potential COVID-19 therapeutic targets.

View the publication

Read Crick news article

Published in Cell systems

Published

Related content

Find out how we share our research, or go in-depth with some reports on particular research areas.

A researcher in a quiet study space at the Crick.

Accessing our research

We are committed to immediate, unrestricted access to our research through open access.
Gloved hands pipetting liquid in HIV lab

Research case studies 

Explore a selection of recent case studies that spotlight particular areas of research at the Crick.