Cambridge Institute for Medical Research

Our strategy

CIMR is a unique partnership between basic and clinical research, aiming to understand the cellular basis of disease. Our goal is to create an inspiring environment in which outstanding scientists can excel. By providing state-of-the-art core facilities and support for our researchers, we foster new collaborations that spark discoveries about fundamental cellular processes and their relevance in disease.

Research Advance

Mutations in the spastin gene are a principal cause of hereditary spastic paraplegia (HSP). Research from the Reid lab has provided new insights into the normal function of spastin, a microtubule-severing ATPase, and the cellular consequences of its loss in HSP. Publishing in Cellular and Molecular Life Sciences, Connell et al show, in cellular models, that spastin interacts with the ESCRT-III-associated proteins IST1 or CHMP1B to prevent cell-polarising membrane protrusions from forming. The protrusions are driven by protrudin, another spastin-interactor. This regulatory control of spastin over protrudin is lost in the absence of spastin, and therefore may contribute to HSP disease pathology.

Research Advance

The advent of CRISPR/Cas9 technology has opened up a growing number of possibilities in genome editing. Paul Manna and Luther Davis from the Robinson and Luzio labs have published a new methodology, CRISPR/Cas9-mediated Homology-independent PCR-product Integration (CHoP-In), in the journal Traffic. Their method enables the generation of 'knock-in' cell lines expressing target proteins N-, C- or internally-tagged with EmGFP / mCherry, without a requirement for donor vectors. Instead, the reporter fusions were generated by PCR and co-transfected directly with the gRNA / Cas9 vector targeting the genes of interest. Positively-expressing cells were separated by flow cytometry and characterised (above left). This method will be used further in the Robinson lab and has already received some wider interest.

Research Advance

Unfolded Protein Response (UPR) effector proteins respond to changing conditions in the endoplasmic reticulum (ER). For example, the ER chaperone BiP is inactivated when AMPylated by FICD, an enzyme which also catalyses BiP’s deAMPylation. In the EMBO Journal, Luke Perera, Steffen Preissler and other colleagues from the Ron and Read labs show that in response to an increase in ER ADP/ATP ratio, FICD switches reversibly from a monomeric AMPylator of BiP to a dimeric state which deAMPylates and thereby activates BiP.

Research Advance

New insights into the molecular cell biology of motor neurone disease (ALS) and related frontotemporal dementias have been published in Cell. In a collaboration between the laboratory of the CIMR's Peter St George-Hyslop, Michael Ward (National Institute of Neurological Disorders and Stroke), Jennifer Lippincott-Schwartz (HHMI Janelia Research Campus), together with other Cambridge colleagues at the Cavendish Laboratory and the Department of Chemistry, Liao et al demonstrated a new mechanism by which RNA granules can be transported on moving lysosomes via Annexin A11. This process can be disrupted by mutations in Annexin A11 that drive certain inherited forms of motor neurone disease.

Research Advances

Membrane phospholipids can be used as fatty acyl donors for the synthesis of triacylglycerols, or fat, by enzymes called PDATs. Antonio Barbosa and colleagues from the Siniossoglou lab present evidence in Dev Cell that, in response to nutrient signals, the yeast PDAT is active at the inner nuclear membrane, providing a link between organelle membrane remodeling and fat storage.

Research Advances

Zuzana Kadlecova and Antoni Wrobel discovered the mechanism by which phosphorylation of the main endocytic adaptor AP2 regulates endocytosis. They observed that this phosphorylation event affects global endocytic rates and they determined its dual role: it favors a new cargo-bound conformation of AP2 and it simultaneously creates a binding platform for accessory proteins. This study was a fruitful collaboration with David Neuhaus (MRC LMB) and Stefan Honing (University Cologne).

Research Advances

Writing in Cell Metabolism, Luis Nobre from Mike Weekes’s lab in collaboration with Ben Gewurz in Harvard Medical School utilize multiplexed proteomics to identify key virus-induced metabolic pathways important for outgrowth of newly infected primary human Bcells. Virus-activated mitochondrial one-carbon metabolism is crucial for nucleotide and glutathione syntheses, as well as generation of intramitochondrial NADPH.

Research Advances

Shenjiang Tan from the Warren lab has reported in Blood that EFL1 mutations impair eIF6 release to cause Shwachman-Diamond syndrome.

Research advances

Vasileios Kargas in the Warren lab (CIMR) has reported in eLife how the key catalytic centre of the ribosome is sculpted.

Research Advances

Writing in Cell Reports, Lior Soday from Mike Weekes’s lab in collaboration with Geoff Smith in the Department of Pathology describe a temporal proteomic analysis of vaccinia virus infection. This includes systematic investigation into virally induced host protein degradation. Vaccinia degrades multiple families of immune ligands and interferon-stimulated genes. The viral C6 protein targets histone deacetylase 5 (HDAC5) for proteasomal degradation to evade the antiviral activity of HDAC5.

IMAGINE ID Family Day

The IMAGINE-ID study, led by Principal Investigator Lucy Raymond at the Cambridge Institute for Medical Research, hosted a Family Fun Day on Sunday 7th July. Avery, the beautiful and touching story written by Professor Raymond, was the theme of the day, with families enjoying plenty of hands-on craft activities, led by Marta Altés, co-author and illustrator of Avery. Marta’s enthusiasm and creativity saw the children make beautifully decorated capes (just like Avery’s), as well as feather bookmarks and wonderful flying birds, which came to adorn a tree mural by the end of the day. The silent disco headsets hired for the event went down a treat with children either dancing away or listening to the music in their own space. Families were also able to take part in a variety of games and puzzles or read the posters displaying the study’s findings. The study’s resident Principal Investigators were also on hand for families needing help or advice. Lucy Raymond said of the family event: “it was a lovely way to say thank you to the families for taking part in the study”

Royal Society Award

Congratulations to Gillian Griffiths who has been awarded the Royal Society Buchanan Medal in recognition of her groundbreaking research establishing the fundamental cell biological mechanisms that drive cytotoxic T-cell (CTL) killing.

World-leading genome study spells hope for sick babies

A Cambridge-based study has shown that the diagnosis and treatment of some of the most critically ill babies can be improved by sequencing their whole genome.

Election to Membership of the European Molecular Biology Organization

Congratulations to Paul Lehner, who has been elected to join 48 Fellows from 17 countries as a member of EMBO. “EMBO Members are excellent scientists who conduct research at the forefront of all life science disciplines, ranging from computational models or analyses of single molecules and cellular mechanics to the study of higher-order systems in development, cognitive neuroscience and evolution,” says EMBO Director Maria Leptin. New Members will be formally welcomed at the annual Members’ Meeting in Heidelberg between 29 and 31 October 2019.

Senior Academic Promotion

Congratulations to Evan Reid who received promotion to University Reader.

A new Director for CIMR

We are delighted to announce that Julian Rayner will become the fourth Director of Cambridge Institute of Medical Research and Professor of Cell Biology, from 1st May 2019. Julian is currently a Senior Group Leader at the Wellcome Sanger Institute and his research focuses on the interactions between Plasmodium parasites and human red blood cells, in order to identify new malaria drug and vaccine targets.

The Keith Peters Building

At 6pm on Thursday 4th April, Professor Sir Keith Peters unveiled a plaque in reception to mark the formal re-naming of our building as The Keith Peters Building. Sixty guests, several of whom held senior positions in the Clinical School over 25 years ago, were invited by the School to be present and somehow, they easily fitted into Reception for the event. Sir Keith, as Regius Professor, was instrumental in convincing the Wellcome Trust and MRC to provide the funds for our building and was also successful in procuring the donation that allowed us to have a lounge/canteen on the top floor. Marking Sir Keith’s Welsh origin, the plaque in Reception is made of Welsh slate and the letter carving is by Kindersley.

Congratulations to David Rubinsztein who has been selected as one of Clarivate Analytics Highly Cited Researchers for 2018. This identifies 6078 scientists and social scientists who have authored multiple highly cited papers that rank in the top 1% by citations for field and year in Web of Science from 2006-2016. The number of researchers selected in each field is based on the square root of the population of authors listed on the field’s highly cited papers.