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

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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.

Mass cytometry images of carcinogen induced lung tumours in mice.

Enzyme target identified to counteract metastasis in pancreatic cancer

This paper addresses the significance of a process called protein palmitoylation for the metastasis of pancreatic cancer cells in immunocompetent mouse models. Metastasis is the major determinant of pancreatic cancer’s extremely poor prognosis, with little known about the mediators of the process. In this paper researchers at the Crick identify a number of novel targets that promote metastasis in vivo, and examine the role of the palmitoyl transferase ZDHHC20, the most prominent of these. Despite having no effect on proliferation or migration in cells in a dish, the loss of this enzyme abolishes metastatic seeding of cancer cells in the body. Interestingly, this effect is reversed in immunodeficient mice and following depletion of immune cells called Natural Killer cells, indicating an interaction with the innate immune system. This manuscript will open avenues for further exploration of palmitoylation-regulated tumour types and provide a basis for development of ZDHHC20-targeting therapeutic strategies that may have value in counteracting metastasis in pancreatic cancer.

Palmitoyl transferase ZDHHC20 promotes pancreatic cancer metastasis

Published in Cell Reports

Published

A modified ZDHHC enzyme and lipid

Solving a lipid whodunnit creates a new class of drug target

Enzymes called ZDHHCs are responsible for directing a type of regulatory modification, palmitoylation, that adds a lipid to specific proteins, but humans have 23 different ZDHHCs, and understanding which proteins each one modifies has been very challenging. A team led by satellite group leader Ed Tate have developed a new method that identifies the set of proteins just one ZDHHC acts on, which has ramifications not just for our understanding of lipid biology, but also for therapeutic strategies targeting proteins whose activity depends on palmitoylation. To progress the research into drug discovery, the researchers have also screened a very large library of compounds to find effective ZDHHC inhibitors.

A palmitoyl transferase chemical-genetic system to map ZDHHC-specific S-acylation

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Published in Nature Biotechnology

Published

Senescent cells

Unravelling the secrets of senescent cells

Ed Tate and Wouter Kallemeijn in the Chemical Biology and Therapeutic Discovery Satellite Lab at the Francis Crick Institute and Imperial College London, in work led by Jesus Gil at the MRC-LMS (Laboratory of Medical Sciences) at Imperial College, have uncovered critical insights that can pave the way for novel therapeutic approaches to tackle cancer, fibrosis, and many age-related conditions. Ed and Wouter identified and patented NMT inhibitors to selectively kill senescent cells, which have stopped growing but can drive inflammation in cancer and fibrosis. Crick/Imperial spin-out Myricx Bio is now developing NMT inhibitors as potential senolytic drugs.

COPI vesicle formation and N-myristoylation are targetable vulnerabilities of senescent cells

Published in Nature Cell Biology

Published

New insights into malaria drug target

A study led by Ed Tate and Tony Holder has looked at how the NMT inhibitor blocks the human malaria parasite, Plasmodium falciparum. The team found at least three mechanisms where inhibition of NMT can disrupt parasite development, and therefore demonstrate the importance of P. falciparum NMT as a drug target.

Inhibition of protein N-myristoylation blocks Plasmodium falciparum intraerythrocytic development, egress and invasion

Published in PLOS Biology

Published

D-Cycloserine destruction by alanine racemase and the limit of irreversible inhibition

D-cycloserine is an antibiotic used for decades to treat drug resistant tuberculosis. Its inhibition mechanism came into question when in a previous paper we determined alanine racemase activity in “fully inhibited” cells. This study demonstrated a previously unknown path during the assumed irreversible inhibition of alanine racemase that leads to the destruction of the antibiotic, meaning that alanine racemase is not irreversibly inhibited by the drug. The paper highlights the complexity of studying the chemical mechanisms of inhibition of enzymes and points to a novel strategy to design D-cycloserine analogues with improved properties.

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Published in Nature Chemical Biology

Published

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Research case studies 

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