A team of six researchers, including Ludwig Oxford’s Sarah De Val and those from Germany and USA, have been awarded a prestigious Fondation Leducq Transatlantic Networks of Excellence Programme grant. These collaborative awards provide $6 million over ﬁve years for work centred on cardiovascular and neurovascular disease. Sarah’s team will characterise the transcription factor Klf2 and its role in blood vessel biology.
Activation of the bacteria-sensing NOD receptors triggers inflammatory signalling via Receptor-interacting protein kinase 2 (RIPK2). Since RIPK2 inhibitors targeting the ATP-binding pocket have been shown to block this signalling pathway, it was assumed that RIPK2 kinase activity was important for signal transmission. In this work published recently in EMBO Journal, Hrdinka, Schlicher and colleagues from Mads Gyrd-Hansen’s lab demonstrate that kinase activity is in fact dispensable for NOD signalling and that these RIPK2 inhibitors are instead preventing the binding of the ubiquitin ligase, XIAP, and the subsequent XIAP-mediated ubiquitination of RIPK2 necessary for downstream signalling. This work could have therapeutic implications since NOD signalling is associated with several chronic inflammatory conditions such as Crohn’s disease.
It is important for cells to control the balance of nutrients – including glucose and amino acids – for proper cell function. A key regulator in this process is the transcription factor, TFEB, which travels to the nucleus upon nutrient limitation to activate the cell’s recycling of unwanted components to restore nutrient levels. Several mechanisms have been described for how nuclear import of TFEB is prevented when nutrient levels are high. In this article published in Nature Communications, Linxin Li, Hans Friedrichsen and colleagues from Prof. Colin Goding’s lab describe an additional control of TFEB cellular localisation. Both amino acid and glucose limitations can alter the phosphorylation status of TFEB in a way that inhibits its nuclear export and thus promotes the activation of cellular recycling. Because deregulation of nutrient levels occurs in many diseases including cancer and neurodegeneration, this work has implications for the development of potential therapeutic interventions.
The 7th Annual CRUK Oxford Centre Symposium was held on 15th June 2018 in the Mathematical Institute, Oxford. The day consisted of a varied programme of presentations, ranging from cancer epidemiology to cancer immunotherapy and ended with an inspiring talk from a patient who has benefited from Oxford’s research via an early phase clinical trial. In addition to the talks, the breadth of cancer research at Oxford was showcased by > 60 posters. ...
Ludwig Oxford’s Sarah De Val was selected to give the prestigious John French lecture at the British Cardiovascular Society Spring Meeting in Manchester. The lecture commemorates the work of John French, a vascular pathologist from the Dunn School of Pathology, Oxford, and is given by an early career scientist of exceptional promise. Sarah talked about her work on blood vessels in development and disease. (Image Copyright Jane Goodall 2018)
In this invited review for Trends in Genetics, Marketa Tomkova and Benjamin Schuster-Böckler explore how epigenetic modification of DNA influences mutagenesis. Some modifications such as methylation of DNA on cytosine bases are well known to increase the rate of mutation through a spontaneous chemical change to thymine. DNA modifications also affect the likelihood of DNA mutagenesis by both external factors e.g. UV light or smoking and cell-intrinsic processes e.g. DNA replication. This review discusses what is known to date and some of the outstanding questions in the field.
It is well known that environmental mutagens are associated with increased cancer risk. However, why cancers of different tissues tend to have their own specific collections of mutations remains unanswered. In a paper published in Nature Communications, Temko et al. from Benjamin Schuster-Böckler’s group have found that whilst mutational processes influence the spectrum of mutations in a cancer, the subsequent selection of certain mutations that give the cancer cell an advantage is also required to give the observed signatures.
On 26th April, Ludwig Oxford hosted the first of the student-organised ‘Distinguished Guest Speaker’ series. Ludwig students, led by Derek Leske from Mads Gyrd-Hansen’s group, voted to invite Salvador Aznar Benitah from IRB Barcelona to talk about his research on stem cell function in homeostasis, aging and cancer. The seminar was followed by a careers advice session over lunch and a dinner at Oriel College in the evening.
The Immunology Symposium, organised by the University of Oxford Immunology Network, showcased the breadth of immunology, infection and inflammation research across the University. The two-day event was held on 16-17th April 2018 at the Mathematical Institute, Oxford and featured a series of talks and poster sessions. Ludwig Oxford’s Prof Mads Gyrd-Hansen spoke about his research on ubiquitin signalling in inflammation and cancer.
The sequencing of RNA from individual cells is an increasingly used, powerful method for studying cellular heterogeneity. However, the analysis of single-cell RNA-seq is limited due to the high technical variability between experiments and the inability to perform true technical replicates on the same cell. David Severson and colleagues from the labs of Benjamin Schuster-Böckler and Xin Lu have developed a new algorithm, BEARscc, published in Nature Communications, which uses simulation to improve the biological interpretation of single-cell RNA-seq experiments.