The 36th European Workshop for Rheumatology Research, February 25-27, 2016 in York, United Kingdom.
Subject: FW: 2015 Jacobson Lecture Friday 25th September - Professor Sir John Savill MBBS FRS PhD, Chief Executive, Medical Research Council
Professor Sir John Savill will be giving the 2015 Jacobson Lecture this Friday 25th September at 5.30pm in the Curtis Auditorium, Herschel Building.
PI Seminar Series
Speaker: Alexandra-Chloé Villani, Broad Institute of MIT and Harvard
Venue: Baddiley Clark Seminar Room
Date: Wednesday 23rd September 2015
Chloe Villani will present:
'Discovery of dendritic cell sub-populations in human blood
by single cell RNA-sequencing'
Following-up a decade of successful disease susceptibility loci identification, the next challenge remains translating these findings to biological understanding of disease. Identifying cells in which these loci are expressed and analyzing individual cells' roles in health and disease are critical to this endeavor. Dendritic cells (DC), which have historically been defined through surface marker analysis, play a critical role in a host's response to pathogens and in the immune responses characterizing cancer, inflammatory and infectious diseases. To discover DC subtypes in a more unbiased approach, we used single cell RNA-seq (scRNA-seq) to profile the transcriptome of 1056 single human blood DCs isolated from a healthy individual. While supervised analysis of DC markers effectively classified the 4 known populations (BDCA2+ (IL3RA), BDCA1+ (CD1C), BDCA3+ (CLEC9A), CD16+ (FCGR3A)), unsupervised analysis re-discovered all 4 subsets through a 630-discriminative gene signature in addition to highlighting novel heterogeneity within subsets. Multi-dimensional classification analysis of the first 384 single cells sequenced identified 26 outlier cells not clustering with any of the 4 known subsets. These outliers displayed a unique expression signature and a shared signature with BDCA2+ and BDCA3+ lineages. Using cell surface markers identified by scRNA-seq, we sorted and validated the existence of these cells in 10 additional healthy donors, showing they represent 0.06% of the PBMCs population in the blood and 2-3% of the DC populations across all 10 donors tested. Isolation and profiling of an additional 384 single cell outliers, together with functional experiments, enabled a deeper characterization of their phenotype. Together these analyses provide a comprehensive view of the DC landscape in blood, revealing new signatures and markers for the 4 known populations, novel subtypes within the known populations, and new rare populations of DCs.
Chair: Dr Muzz Haniffa
Prof Dieter Brömme
Canada Research Chair in Proteases and Diseases, University of British Columbia, Faculty of Dentistry, Vancouver, Canada
CHANGED to L3.2
Friday 4th September 2015
12.00 – 1.00pm
Prof Dieter Brömme will present:
‘Extracellular Matrix Degradation by Cathepsins’
Extracellular matrix degradation is thought to be catalyzed by matrix metalloproteases as they are active at neutral pH, secreted or localized at plasma membranes, and efficient in degrading matrix proteins. However, recent research has revealed that lysosomal acidic cysteine proteases such as cathepsins are critical for bulk matrix protein turnover and that they significantly contribute to various extracellular matrix related pathologies such as osteoporosis, arthritis, atherosclerosis, destructive lung diseases, cancer and skin disorders. Cysteine proteases such as cathepsins K, S, and V represent arguably the most potent mammalian collagenases and/or elastases. The presentation will provide structural explanations for their matrix protein-degrading activities, discuss the role of these enzymes in bone and vascular diseases, and characterize them as effective therapeutic targets. A novel approach of selectively inhibiting the collagenase and elastase activity of cathepsins without interfering with other activities will be discussed using cathepsin K as an example.
Chair: Prof Drew Rowan
Please let Drew Rowan (firstname.lastname@example.org) know if you would like to speak to Dieter in the afternoon after the talk.