Seminar Lucas Pelkman – Tuesday November 17, 2015 (14.00, 8th floor RIMLS)

On Tuesday November 17, 2015, dr. Lucas Pelkman from the Institute of Molecular Life Sciences of the University of Zurich (Switzerland) will give a presentation entitled “Origins of cellular heterogeneity” at 14.00 in the Figdor Lecture theatre on the 8th floor of the RIMLS building.

lucas Pelkman

Cells do not operate in isolation, but create heterogeneous social contexts, to which they adapt their phenotypic behavior. This is true for single-cell organisms as well as for cells from multicellular organisms. The effect of this type of cell-to-cell variability on shaping the phenotypic spectrum of single cells has major consequences for how we study cellular processes and interpret molecular mechanisms and activities in single cells. It also shows that basic social properties of mammalian cells can be studied in in vitro experimental systems using cells grown in culture.

Key publications:

Cell-intrinsic adaptation of lipid composition to local crowding drives social behaviour. Nature; 523:88-91, 2015
A hierarchical map of regulatory genetic interactions in membrane trafficking. Cell; 157:1473-87, 2014
Image-based transcriptomics in thousands of single human cells at single-molecule resolution. Nat Methods; 10:1127-33, 2013

Seminar Chris Bakal – Tuesday October 6, 2015 (14.00, 8th floor RIMLS)

On Tuesday October 6, 2015, dr. Chris Bakal from the Institute of Cancer Research, London (UK) will give a presentation entitled: “Using statistical cell biology to understand the emergence of phenotypic heterogeneity in cancer cell populations” at 14.00 in the Figdor Lecture Theatre on the 8th floor of the RIMLS building.

chris-bakal

Dr. Chris Bakal’s Dynamical Cell Systems Team uses genomic approaches and computational modelling to understand how complex biochemical signalling networks are ‘rewired’ during the development of cancer.

Key publications

  • A screen for morphological complexity identifies regulators of switch-like transitions between discrete cell shapes. Nat Cell Biol. 2013.
  • Visualizing cellular imaging data using PhenoPlot. Nat Commun. 2015.
  • Cell shape and the microenvironment regulate nuclear translocation of NF-κB in breast epithelial and tumor cells.  Mol Syst Biol. 2015.

Seminar Tamar Geiger – Wednesday September 23, 2015 (09.30, 8th floor RIMLS)

On Wednesday September 23, 2015, dr. Tamar Geiger from the Tel Aviv University, Israel  will give a presentation entitled: “System-wide clinical proteomics of breast cancer reveals global remodeling of cellular homeostasis” at 09.30 in the Figdor Lecture Theatre on the 8th floor of the RIMLS building.

tamar

The genomic and transcriptomic landscapes of breast cancer have been extensively studied, but the proteomes of breast tumors are far less characterized. In recent years, developments in mass spectrometric technology, sample preparation techniques and computational analysis opened new possibilities for genome-scale proteomic analysis of clinical samples. We used the recently developed super-SILAC mix, which is a mixture of lysates of five SILAC-labeled cell lines that serves as an internal standard for accurate tissue quantification. Combined with high-resolution, high-accuracy mass spectrometry we performed a deep analysis of breast cancer progression using clinical breast samples from lymph node negative and lymph node positive luminal tumors, as well as matched lymph node metastases and healthy breast epithelia. We quantified over 10,000 proteins with high accuracy, enabling us to identify key proteins and pathways that regulate tumorigenesis and metastatic spread. Surprisingly, we found an anti-Warburg effect dominating the metabolic changes, in which the cancer cells show higher oxidative phosphorylation and lower glycolytic activity. In addition, we extracted a 65-protein signature that predicts lymph node involvement based solely on the primary tumor, which may hold important clinical significance in disease management and treatment.

Seminar Michael Lund Nielsen – Thursday September 17, 2015 (Hippocrates room, route 77)

On Thursday September 17, professor Michael Lund Nielsen from the University of Kopenhagen will give a seminar entitled “Systematic and quantitative analysis of the human arginine methylome”. The seminar will be held from 10.00-11.00 in the Figdor Lecture Theatre in the Hypocrates room, route 77.

nielsen

Post-translational modifications (PTMs) greatly increase the complexity of proteins far beyond the combinatorial possibilities of the twenty amino acids. As a result, the ability to characterize and identify PTM patterns in cells, tissues and organisms on a proteome-wide scale has become important to better understand the molecular details of the individual PTMs and their associated enzymes. Arginine methylation is a PTM that increases the structural diversity of proteins and modulates their function in living cells. Methylation of the arginine side-chain is catalyzed by protein arginine methyltransferases (PRMTs), many of which are able to generate both omega-N-methylarginine (MMA; arginine mono-methylation) and asymmetric/symmetric N,N-dimethylarginine (ADMA/SDMA; arginine di-methylation) on target proteins. Although discovered 50 years ago, protein methylation has predominantly been studied as a mechanism of epigenetic regulation of histones, while reports describing arginine methylation on non-histone proteins has only started to emerge in recent years. Here we describe an improved proteomic strategy for proteome-wide characterization of arginine methylation in human cells. Using the developed methodology we identify 9.000 arginine methylation sites on >3.300 human proteins, demonstrating that arginine methylation is a wide-spread modification similar to phosphorylation and ubiquitylation. Using RNAi experiments of various PRMT enzymes we are able to characterize the specific substrates targeted by these enzymes using quantitative proteomics. Collectively our proteomics strategy allows for novel insights into the human arginine methylome.

Seminar Robert Schneider – Tuesday September 8, 2015 (14.00, 8th floor RIMLS)

On Tuesday September 8, dr. Robert Schneider will give a seminar entitled: “Novel players in chromatin”. The seminar will be presented at 14.00 in the Figdor Lecture Theatre on the 8th floor of the RIMLS building.

schneider

Robert Schneider is group leader at the Institute of Genetics and Molecular and Cellular Biology (IGBMC), Strasbourg, France. His team focusses on medical epigenetics, with a long-term aim to apply mechanistic insights towards therapy, e.g. by identifying novel therapeutic targets or new diagnostic markers. They are currently identifying and studying new histone modifications. The team is deciphering how these modifications are inherited, how they regulate gene expression/chromatin dynamics, and in particular their role in disease processes such as cancer. Whilst it is still under discussion if histone modifications form a true “code”, it has now been established that changes of histone modifications (and of their ”readers”) are involved in the regulation of all genes and as such can initiate disease processes. Therefore the significance of studying chromatin modifications extends far beyond the field of chromatin research and has clear medical relevance.