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Tuesday, September 19
 

8:00am

Welcome Coffee Break
Tuesday September 19, 2017 8:00am - 9:00am
Foyer Courtyard by Marriot Madrid Princesa Hotel

8:00am

Registration Open
Tuesday September 19, 2017 8:00am - 5:00pm
Foyer Courtyard by Marriot Madrid Princesa Hotel

9:00am

Exhibitor Tutorial
Tuesday September 19, 2017 9:00am - 11:00am
Rosales I Courtyard by Marriot Madrid Princesa Hotel

9:00am

Exhibitor Tutorial
Tuesday September 19, 2017 9:00am - 11:00am
Galileo III Courtyard by Marriot Madrid Princesa Hotel

11:00am

Welcome and Opening Remarks
Moderators
Tuesday September 19, 2017 11:00am - 11:05am
Rosales I Courtyard by Marriot Madrid Princesa Hotel

11:00am

Exhibition Open
Tuesday September 19, 2017 11:00am - 8:00pm
TBA

11:05am

Session 1: Technology
Microscopy is fast evolving field with development in resolution, imaging modalities, flexibility of acquisition and much more. This session will show how some of these exciting advances are being applied in automated screening setups to allow screening more complex cellular systems for higher clinical relevance.

11:05 - 11:30:
Droplet-Microarray – a miniaturized platform for high throughput screenings
Anna Popova, Institute for Toxicology and Genetics, Karlsruhe Institute of Technology

Phenotypic high throughput screening (HTS) of live cells is a methodology that lies at the basis of fundamental research, drug discovery and toxicology. The main problematic of screenings in our days lies in relatively large volumes per experiment and at the same time a need for higher throughout. Miniaturization of high throughput screenings has been a major trend in past years. Since further miniaturization of microtiter plates is not possible, alternative technologies are emerging to address this problem. Here we present a Droplet-Microarray (DMA) platform - a novel miniaturized platform for HTS of live cells. DMA consists of an array of superhydrophilic spots on superhydrophobic background. Due to extreme difference in wettability between superhydrophilic and superhydrophobic areas cell suspension applied on such surface spontaneously splits in array of homogeneous separated droplets of nL volumes, enabling pipetting-free seeding of cells. We have developed protocols for parallel addition of compounds and reagents simultaneously to the whole array without a need for pipetting of each individual compartment. The DMA platform is transparent and compatible with all kinds of microscopy. In addition, the DMA has dimensions of microscope glass slide or microtiter plate and, therefore, is compatible with all existing microscopes. All the standard protocols including staining, fixation and immunofluorescence can be performed on DMA platform, making it easy to incorporate it into existing screening workflows. In the past years we have evaluated DMA platform for cell-based screening applications. We successfully cultured over 10 different adherent and suspension cell lines, stem cells and primary patient-derived cells in miniaturized format. We have established protocols for transfection and compound treatment of cells on the DMA platform. We optimized procedures for staining, fixation and microscopy of cells of suspension and adherent nature. We tested DMA platform in a proof-of-concept screen on primary patient-derived tumor cells with antineoplastic compounds. We evaluated DMA platform for screening of cells in 3D environments by means of hydrogels, spheroids and embryonic bodies. Moreover, we further extended the portfolio of applications of DMA platform to whole – organism screenings. Using DMA platform we created single-embryo-array where single zebrafish embryo is trapped in an individual droplet, and evaluated this array for toxicity screening applications. Single-embryo-array based on the DMA principle enables detailed microscopic analysis of embryos, which are fixed in particular position in array format, significantly simplifying imaging process and image analysis of live animals. We believe that DMA technology carries a great potential to be adopted for various high content screening applications. On one hand, it is flexible and universal due to its compatibility with various cell types, different functional assays, standard protocols and all types of microscopy. On the other hand, it is highly miniaturized (3-80 nL) and pipetting-free. Thus, the DMA platform is a chip technology for cell-based assays that enables miniaturized and parallelized high throughput screenings of live cells in 2D and 3D, as well as whole-organisms.

11:30 - 12:00:
Multiscale cytometry and regulation of 3D cell cultures on a chip
Charles Baroud, Ecole Polytechnique

Three-dimensional cell culture is emerging as a more relevant alternative to the traditional two-dimensional format. Yet the ability to perform cytometry at the single cell level on intact three-dimensional spheroids or together with temporal regulation of the cell microenvironment remains limited. I will describe a microfluidic platform to perform high-density three-dimensional culture, controlled stimulation, and observation in a single chip. The method extends the capabilities of droplet microfluidics for performing long-term culture of adherent cells. Using arrays of 500 spheroids per chip, in-situ immunocytochemistry and image analysis provide multiscale cytometry that yields information at the population scale, at the scale of 10,000 or more single spheroids, and nearly 1,000,000 single cells. This allows us to correlate functionality with cellular location within the spheroids and the local structure. Also, an individual spheroid can be extracted for further analysis or culturing. Then by combining this approach with a more advanced droplet handling approach, I will demonstrate how a complete drug response curve can be obtained in a single sweep on a chip. This approach will enable a shift towards quantitative studies on three-dimensional cultures, under dynamic conditions, with implications for stem cells, organs-on-chips, or cancer research.

12:00 - 12:30:
Cancer organoids for screening of chemotherapeutics and personalized medicine
Francesco Pampaloni, Buchmann Institute for Molecular Life Sciences (BMLS)

Three-dimensional (3D) cell cultures allows establishing physiologically relevant in vitro tissue models, which are of great interest for both industry and clinical research.  In my talk, I describe two 3D cell culture platforms for drug screening based on live fluorescent microscopy recently developed in our group. The first platform is based on U343 glioma 3D multicellular spheroids, which represent a realistic brain cancer model. With the U343 spheroids we established a drug screening pipeline for the identification of autophagy modulators. Since the autophagic flux is often dysregulated in cancer, the discovery of novel autophagy modulating drugs is of great clinical relevance. This screening assay with 3D tumor spheroids is robust, reproducible and scalable and represents a valuable tool for both basic research and pharmaceutical industry [1].The second drug screening platform uses hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) stem cell organoids. The tumor stem cell organoids are obtained from liver biopsies and can be virtually limitless expanded in culture [2]. I illustrate the pros and contra of this new technology and our pipeline for the testing of chemotherapeutics with high-throughput microscopy, discuss realistic approaches for a personalized cancer therapy, and show first data recorded with Light Sheet Fluorescence Microscopy (LSFM). 

12:30 - 13:00:
Combining high-content imaging and pathway profiling technologies to advance in vitro pharmacogenomics and discovery of novel drug combinations
Neil Carragher, Institute of Genetics and Molecular MedicineUniversity of Edinburgh

Recent advances in high-content screening, CRISPR/Cas-based genome editing and induced pluripotent stem cell technologies are converging to stimulate the new discipline of Phenomics Drug Discovery. I will describe how Phenomics Drug Discovery incorporates state-of-the-art imaging, genomics, proteomics and informatics tools to explore drug mechanism-of-action (MOA) studies across genetically defined in vitro cell models. We demonstrate how multiparametric high content screening assays combined with novel image-informatics and machine learning methods advance in vitro pharmacogenomic studies across a broader variety of phenotypes, disease models and therapeutic classes. We also demonstrate how ultrasensitive Reverse Phase Protein Microarray (RPPA) technologies can combine with imaging to characterize drug MOA at the post-translational pathway network level. Finally, I present recent examples of how our Phenomics Drug Discovery platform enabled the rapid discovery of a novel orally-available, ATP-competitive, kinase inhibitor and novel drug combinations which display potent anti-tumour activity across 2D, 3D and in vivo models.

13:00 - 13:30:
Applications of non-invasive phenotypic screens using label free imaging by digital holography; three selected examples
Gerardo Turcatti, EPFL 

In the fast evolving field of screening by imaging, a main challenge is to conciliate complex models or assays with more in vivo relevance and throughput. In this context, we are developing assays with representative cells or models amenable to screening using holographic microscopy (DHM) for imaging cells. DHM is a label-free interferometric microscopy technique, which provides a quantitative measurement of the optical path length. It is a two-step process where a hologram consisting of an interference pattern is first recorded on a digital camera and the quantitative phase images are reconstructed numerically using a specific algorithm. We illustrate here three phenotypic screening applications using DHM as imaging read-out: a) a drug screening method for adipocytic differentiation through lipid quantification b) a screen for quantification of cardiomyocytes beating dynamics c) a screening assay for measuring trans-epithelial fluxes in CFTR mutations using gastrointestinal-derived...

Moderators
avatar for Marc Bickle

Marc Bickle

Head TDS, MPI-CBG
Dr. Marc Bickle obtained his PhD title at the Biozentrum of the University of Basel Switzerland in the laboratory of Prof Michael N Hall studying the mode of action of the immunosuppressive drug Rapamycin using yeast as a model system After receiving his degree he went to the Lab... Read More →

Speakers
avatar for Charles Baroud

Charles Baroud

Ecole Polytechnique
Charles Baroud was trained as a physicist and engineer at MIT, then received a PhD at the University of Texas at Austin. Since then he has founded and now leads the microfluidics group at Ecole Polytechnique in Paris. The group has performed fundamental fluid dynamics research on... Read More →
avatar for Francesco Pampaloni

Francesco Pampaloni

Francesco Pampaloni is staff scientist with permanent position at the Buchmann Institute for Molecular Life Sciences (BMLS) in Frankfurt am Main (Germany). He leads the research on three-dimensional cell cultures and he is coordinator and scientific manager of the EU Horizon 2020 project LSFM4LIFE. He graduated in Physical Chemistry at the University of Florence (Italy). Awarded with an EU Marie-Curie Fellowship programme, he moved to the University of Regensburg (Germany), where he obtained his Ph.D. with excellence with a work on Optical Force Microscopy. From 2003 to 2009 post-doc and staff scientist at EMBL Heidelberg (Germany). Since 2010 at the Buchmann Institute for Molecular Life Sciences (BMLS) of the Goethe University Frankfurt. He authored 40+ publications and four patents. He is main inventor and driving force of the High-Throughput LSFM (HT-LSFM) and the Tissue Culture LSFM... Read More →
avatar for Anna Popova

Anna Popova

Institute for Toxicology and Genetics, Karlsruhe Institute of Technology
avatar for Gerardo Turcatti

Gerardo Turcatti

Director of the Biomolecular Screening Facility, EPFL
Dr. Gerardo Turcatti directs the Biomolecular Screening Facility (BSF) he created at the EPFL in 2006. In the frame of the National program NCCR-Chemical Biology, he leads the project ‘ACCESS’ ‘An Academic Chemical Screening Platform for Switzerland’ since 2011. Previously he co-founded and acted as CTO of Manteia S.A., a Swiss-based company that developed revolutionary high throughput DNA sequencing technologies currently commercialized by Illumina Inc. Prior to this experience, Dr Turcatti had a long multidisciplinary career in... Read More →


Tuesday September 19, 2017 11:05am - 1:30pm
Rosales I Courtyard by Marriot Madrid Princesa Hotel

1:30pm

Lunch Break in Exhibition
Tuesday September 19, 2017 1:30pm - 2:30pm
Rosales 2+3 Courtyard by Marriot Madrid Princesa Hotel

2:30pm

Session 2: Screens
Thanks to recent advances in cell culture and imaging technologies, high content screenings are now reaching a critical point where they can be realistically deployed at large scale, opening exciting opportunities for industry and academia. This section aims to gather worldwide experts involved in every aspects of this promising field to share their recent achievements and vision of the future.

2:30 - 3:00
Filling the Drug Discovery Gap: Is HCS the Missing Link?
Jean-Philippe Stéphan, SERVIER

Despite the fact that many drugs on the market today were discovered through phenotypic screens, this approach is considered by many investigators as a “black box” and in many cases target centric biochemical or cellular assays are preferred to support the initial drug discovery steps. Nevertheless, this “white box” approach clearly does not deliver all the expected success in term of drug developments, mostly due to the lack of pathophysiological relevance of the models. Now, the pharmaceutical industry is implementing new discovery paradigms to try to solve the current disconnect between the drug discovery process and the human clinical trials. Among the myriad of new technologies and approaches currently considered, High Content Screening combined with biosensors technologies, genome-editing and stem cell-derived cellular models offer the opportunity to drastically transform phenotypic screening, linking target engagement and phenotypic impacts in more relevant in vitro models. This new generation phenotypic screens combined with the current drug discovery strategies represent a true opportunity to fulfill the gap between the screening dish and the patients. Despite the tremendous potential of HCS, researchers have to carefully consider various aspects of the projects before deploying the technology and this presentation will go through several examples highlighting the current strengths and weaknesses of the approach.    
3:00 - 3:30  
Imaging Phenomics for the Discovery of Next-Generation Anti-Virals
Steffen Jaensch, Janssen Pharmaceutica

Several proof-of-concept studies have demonstrated that unbiased pheno-signatures derived from high-content imaging data provide a powerful tool to characterize the mechanism-of-action of small molecules in a cellular context. Such signatures can be generated at an early stage of the drug discovery pipeline and provide valuable information to guide, for example, the selection of lead compounds from high-throughput screening hits. We have employed such a phenomics approach for the discovery of novel anti-viral compounds. We established an imaging assay and computational pipeline to generate pheno-signatures that capture the infection state and morphological characteristics of single cells under compound treatment. The signature of non-infected untreated cells describes the most desirable phenotypic state that an ideal inhibitor should revert infected cells back to. We validated our approach with annotated reference compounds and found that we can distinguish host-factor targeting from direct anti-viral compounds with near perfect accuracy. Our method can also distinguish several sub-categories of direct anti-viral mechanisms such as replication vs. entry inhibitors. This greatly reduces the need for costly and time-consuming follow-up assay cascades.

3:30 - 4:00 
High-content phenotypic screening using disease relevant, human, primary cells – Identifying and profiling diverse compounds for cardiac regeneration
Erik Müllers, AstraZeneca

Heart failure is incapacitating and currently incurable. It is thought that activation and proliferation of resident cardiac progenitor cells, i.e. EPDCs has therapeutic potential to help repair the heart after injury. However, drug discovery approaches have so far been impeded by lack of well-defined screening platforms and poor understanding of the molecular mechanisms regulating EPDC activation, proliferation and differentiation. In areas of novel and complex pharmacology high-content phenotypic screening is particularly attractive to identify starting points for potential therapeutics in an unbiased fashion, as well as to aid target deconvolution and mechanism of action activities. We developed and validated a high-throughput, phenotypic screen for compounds selectively proliferating EPDCs while maintaining the progenitor phenotype. Following from the primary screen and respective counter screens we identified and validated hits representing more than 20 different chemical clusters. For a few of these cluster we could identify primary targets. To further aid target identification and mode of action studies we applied a high-content image-based assay for morphological profiling, i.e. Cell Painting, to our EPDC screening campaign. The assay was implemented in 384-well format, using automated liquid handling, high-throughput microscopy, and automated image analysis on a high-performance computing cluster. Building on available image analysis pipelines for nucleus, cell and cytoplasm we developed additional segmentation of endoplasmic reticulum and nucleoli. From the segmented objects thousands of cellular features were extracted and analysed using clustering algorithms resulting in morphological fingerprints of donor populations, and effects of compound treatment. In summary, we developed a high-throughput phenotypic screen as well as a high-content phenotypic screen using relevant human primary cells. We used the assays to identify starting points for drug discovery projects, to better understand mechanism of action, and to deconvolve primary drug targets.

4:00 - 4:30
Genome-wide RNAi screening combined with high content imaging to dissect membrane traffic pathways in mammalian cells
Jez Simpson, University College Dublin

The endomembrane system of mammalian cells has a unique architecture allowing it to carry out a large number of specialised biochemical reactions in parallel. The function of these organelles is dependent on highly regulated intracellular transport events between them. We are using a systematic approach of genome-wide RNA interference screens combined with high-content screening (HCS) microscopy, specifically applying texture feature analysis and machine learning, to quantitatively map these transport pathways and identify their regulators. In this seminar I will describe how this approach has revealed novel regulators of the endomembrane system, and regulators of how nanoparticles (as surrogate drug delivery vectors) enter and traffic through cells. I will also discuss some of the challenges associated with transitioning membrane traffic assays between 2D and 3D cell culture formats.
Overall, the information that we gather provides a deeper systems-level view of how cells are organised, and provides knowledge fundamental to the design of next generation drug delivery vectors and biomedical devices. 

[1] Galea G, Bexiga MG, Panarella A, O'Neill ED & Simpson JC (2015). A high-content screening microscopy approach to dissect the role of Rab proteins in Golgi-to-ER retrograde trafficking. J. Cell Sci., 128(13), 2339-2349.
[2] Panarella A, Bexiga MG, Galea G, O' Neill ED, Salvati A, Dawson KA & Simpson JC (2016). A systematic High-Content Screening microscopy approach reveals key roles for Rab33b, OATL1 and Myo6 in nanoparticle trafficking in HeLa cells. Scientific Reports, 6, 28865.

4:30 - 5:00 
Presentation Title Forthcoming
Michael Boutros, Deutsches Krebsforschungszentrum

Speakers
avatar for Steffen Jaensch

Steffen Jaensch

Senior Scientist, Johnson & Johnson
Dr. Steffen Jaensch works at Janssen Pharmaceutica, Pharmaceutical Companies of Johnson & Johnson, in Beerse, Belgium. He is responsible for the analysis of imaging assay development and screening data for drug discovery and target identification projects with a focus on establis... Read More →
avatar for Jez Simpson

Jez Simpson

Jeremy Simpson carried out his PhD at the University of Warwick (UK). After post-doctoral work at the Scripps Research Institute (San Diego, USA) and the ICRF (London, UK), a long term EMBO fellowship took him to the EMBL (Heidelberg, Germany), where he developed and applied novel high-throughput imaging approaches to study protein localisation and membrane traffic. In 2008 he was appointed as Professor of Cell Biology at University College Dublin, Ireland. His lab applies high-throughput imaging technologies to study intracellular trafficking pathways, the internalisation routes taken by synthetic nanoparticles on exposure to cells, and how cells respond to nanomaterials and nanosurfaces. He has authored over 90 peer-reviewed articles, including articles in Nature Cell Biology, Nature Communications and Nature Methods, and runs the UCD Cell Screening Laboratory (www.ucd.ie/hcs). He is currently the Head of School of Biology... Read More →
avatar for Jean-Philippe Stephan

Jean-Philippe Stephan

Head of Models & HTS department, Institut de Recherches Servier
Jean-Philippe Stéphan, originally from Rennes, Brittany, France, received his Ph.D. in Developmental Biology from Pierre and Marie Curie University (Paris VI, France). After a postdoctoral fellowship at Genentech, he was hired as a Research Scientist in the Assay and Automation Technology department (AAT) at Genentech, Inc. Over his 17 years tenure at Genentech, Dr... Read More →


Tuesday September 19, 2017 2:30pm - 5:00pm
Rosales I Courtyard by Marriot Madrid Princesa Hotel

5:00pm

Coffee Break in Exhibition
Tuesday September 19, 2017 5:00pm - 5:30pm
Rosales 2+3 Courtyard by Marriot Madrid Princesa Hotel

5:30pm

Poster Presentation Talks
Tuesday September 19, 2017 5:30pm - 6:30pm
Rosales I Courtyard by Marriot Madrid Princesa Hotel

6:30pm

Networking Reception in Exhibition
Tuesday September 19, 2017 6:30pm - 8:00pm
Rosales 2+3 Courtyard by Marriot Madrid Princesa Hotel
 
Wednesday, September 20
 

8:00am

Exhibition Open
Wednesday September 20, 2017 8:00am - 3:30pm
Rosales 2+3 Courtyard by Marriot Madrid Princesa Hotel

8:00am

Registration Open
Wednesday September 20, 2017 8:00am - 3:30pm
Foyer Courtyard by Marriot Madrid Princesa Hotel

8:30am

Morning Coffee Break
Wednesday September 20, 2017 8:30am - 9:00am
Foyer Courtyard by Marriot Madrid Princesa Hotel

9:00am

Session 3: Data Analysis
The analysis of the large amount of data generated high content screening experiments represents a significant challenge and is currently a bottleneck in many small molecules and genetic screening projects.  This section is an exciting opportunity for reviewing the main challenges in interpreting complex high-content screening data, including key informatics and data analysis approaches such as image descriptors computations and classification algorithms.

9:00 - 9:30 
Computational methods for fluorescence microscopy and quantitative bioimaging
Charles Kervrann, Senior Researcher, Inria Rennes - Bretagne AtlantiqueSEPICO Project-Team 

During the past two decades, biological imaging has undergone a revolution in the development of new microscopy techniques that allow visualization of tissues, cells, proteins and macromolecular structures at all levels of resolution. Thanks to recent advances in optics, digital sensors and labeling probes, one can now visualize sub-cellular components and organelles at the scale of a few dozens nanometers to several hundreds of nanometers. As a result, fluorescent microscopy and multimodal imaging has become the workhorse of modern biology. All these technological advances in microscopy, created new challenges for researchers in quantitative image processing and analysis. Therefore, dedicated efforts are necessary to develop and integrate cutting-edge approaches in image processing and optical technologies to push the limits of the instrumentation and to analyze the large amount of data being produced.In this talk, we present image processing methods, mathematical models, and algorithms to build an integrated imaging approach that bridges the resolution gaps between the molecule and the whole cell, in space and time. The presented methods are dedicated to the analysis of proteins in motion inside the cell, with a special focus on Rab protein trafficking observed in time-lapse confocal microscopy or total internal reflection fluorescence microscopy. Nevertheless, the proposed image processing methods and algorithms are flexible in most cases, with a minimal number of control parameters to be tuned. They can be applied to a large range of problems in cell imaging and can be integrated in generic image-based workflows, including for high content screening applications.

9:30 - 10:00 
Big data approaches for computational phenotyping
Thomas Walter, MINES ParisTech 

In High Content Screening (HCS) we dispose of the technological tools to perform imaging experiments at an unprecedented scale and thus to generate extremely large and complex image data sets, that can be readily qualified as “big data”. In this context, methods from computer vision and machine learning have been instrumental to deal with the generated large-scale image data sets. After a short review of computer vision techniques for computational phenotyping for live cell imaging data, I will present recent developments in the field of spatial transcriptomics, where we aim at understanding the spatial aspects of gene expression at a large scale. This poses interesting and challenging questions for the analysis of such data: single RNAs can be automatically detected and their spatial distribution analyzed with newly designed features and machine learning methods. Importantly, as there is little prior knowledge available for this type of data, we have built a virtual cell environment in order to simulate RNA localization patterns inside cells to validate the developed methods. More generally, simulation frameworks are becoming increasingly important for computational phenotyping. Finally, I will present new approaches to analyze and computationally phenotype cells in their tissular context. Segmentation is one of the major bottlenecks in computational phenotyping of histopathology data. Here, I present a new technique for the segmentation and classification of nuclei based on deep learning. This method allows us to analyze large cohorts of patient data with respect to their cellular and tissular phenotypes and to relate these descriptors to clinical variables.

10:00 - 10:30
Presentation Title Forthcoming
Marco Prunotto, Roche

10:30 - 11:00
Presentation Title Forthcoming
Lucas Pelkmans, University of Zurich, Institute of Molecular Life Sciences

11:00 - 11:30
Exploring Toxicity Profiling for Drug Screening using Deep Learning Strategies
Daniel Jimenez, Centro Nacional de Investigaciones Cardiovasculares (CNIC)

Toxicity is a major factor of failure in drug development, causing costly withdrawals of drugs from the market. Efficienct drug discovery could be greatly improved if compounds with cytotoxic characteristics were identified during primary screening campaigns. Although apoptotic & necrotic processes involve dramatic changes in cell morphology, these have never been exploited for systematic and quantitative assessment of cellular toxicity due to lack of methods to identify them in a reproducible manner. The development of high-content imaging platforms has allowed the incorporation of complex toxicity counter-screens. However, this requires expensive and lengthy labelling of cytotoxicity specific reporters. There is thus an urgent need to develop cost-effective methods for toxicity assessment qualified for high throughput screening (HTS). We hypothesize that toxicity could be detected without toxicity specific labelling by using state of the art computer vision methods, thus reducing significantly the cost of drug screens. In this work we develop a framework to determine cell cytotoxicity status as a HTS readout based on the analysis of nuclear fluorescence microscopy images by using deep learning strategies. Multiple cell-based assays including concentration-response curves for drugs with different cytotoxic effects are used for training and validation of the system. Preliminary results support our hypothesis, reporting high correlations between toxicity predictions, dose-response curves, and well-established cytotoxicity reporters; suggesting that the automatic pattern recognition performed by deep neural networks is able to detect differential structural and nuclear-based features related with the cytotoxic state of the cells. Therefore, this framework has the potential to become a new scientific breackthrough for toxicity assessment in drug screening.


Speakers
avatar for Charles Kervrann

Charles Kervrann

Inria Senior Researcher, Inria Rennes - Bretagne Atlantique
Charles Kervrann received the M.Sc. (1992), the PhD (1995) and the HDR (2010) in Signal Processing and Telecommunications from the University of Rennes 1, France. From 1997 to 2010, he was researcher at the INRA Applied Mathematics and Informatics Department (1997-2003) and he... Read More →
avatar for Thomas Walter

Thomas Walter

Thomas Walter has been working in the field of biomedical image analysis for more than 15 years. His most visible scientific contributions have been in the field of High Content Screening (HCS). He has pioneered methods in the field of cellular phenotyping for live cell imaging d... Read More →


Wednesday September 20, 2017 9:00am - 11:30am
Rosales I Courtyard by Marriot Madrid Princesa Hotel

11:30am

Coffee Break in Exhibition
Wednesday September 20, 2017 11:30am - 12:00pm
Rosales 2+3 Courtyard by Marriot Madrid Princesa Hotel

12:00pm

Session 4: Model Systems
The selection of a suitable model system is critical in the successful advancement of novel therapeutic approaches to disease. The development of models and assays that recapitulate the full complexity of the disease they intend to represent, and the ability to scale them up to screening campaigns remains a big challenge in the field. The session will bring together experts in the field presenting innovative models across different disease areas. 

12:00 - 12:30 
Presentation Title Forthcoming
Marc Mercola, Stanford University 

12:30 - 1:00 
Combining functional genomics screening, 3D models and multiparametric phenotypic analysis supports identification of selected ARF GTPases as modulators of polarity and invasion.
Emma Shanks, Cancer Research UK Beatson Institute

The utility of 3D models in high throughput screening, high content imaging and phenotypic analysis is currently a topic of much discussion. Here we present data from a screen investigating ARF GTPases, regulators and effectors in a prostate cancer spheroid model. We conducted a screen using a bespoke library of shRNAs which co-expressed a fluorescent tag to allow for intrawell phenotype normalisation between infected and non-infected spheres. Multiparametric phenotypic image analysis was utilised to identify, teach and quantify phenotypes pertaining to polarity, in conjunction with 'standard' morphological analysis. All screening was conducted in 2D and 3D, with the latter evaluated using fixed and live cell imaging. Informatics was employed to introduce streamlined data handling workflows, based principally on KNIME, to allow interpretation of data-rich phenotypic analysis. Target deconvolution and validation approaches identified specific ARF GTPases as modulators of polarity and potential therapeutic targets for metastatic disease. We have conducted i) 2D vs 3D and ii) 3D fixed vs live cell inter-platform comparisons. This has provided insights into the value of each model system, but moreover, has allowed us to explore the phenotypic consistencies between models, and therefore their predictive power. In particular, we identified a combination of phenotypes which, when present in 3D fixed cells, successfully predict invasive potential, which we validated using longer-term, live cell assays. These findings will be discussed.



1:00 - 1:30 
Presentation Title Forthcoming 
Christian Helker, Max Planck Institute

Historically, screens to identify small molecules are done through target and phenotypic based in vitro screens.  However, the identified drugs often fail in the preclinical animal model for two main reasons: 1) pharmacokinetics at the whole organism level, including the absorption, distribution, metabolism, and excretion (“ADME”) properties of small molecules2) cytotoxicity and side/off target effects.  These complexities hinder the extrapolation of drug-target interactions in vitro to pharmacological actions in vivo, resulting in more than 70% of compounds in oncology to fail in phase II clinical trials, while 59% of the remaining compounds are discarded in phase III due to intolerable toxicities.Considering these challenges, developing tools for rapid, cost-efficient and translational small-molecule discovery in whole organisms greatly strengthens the translation potential in novel drug discovery. Zebrafish embryos are amenable to semi high-throughput chemical screens combining the advantages of the scale of in vitro screens with the physiological complexity of a developing animal. Using the zebrafish as an in vivo system for drug discovery has several unique advantages: (i) the low cost per animal, (ii) ease of genetic manipulations  (iii) small body size enables to screen zebrafish larvae in 96-well plates (iv) large progeny of embryos to ensure high throughput of large chemical libraries (v) as a vertebrate, the zebrafish shares a similar body plan to mammals and genetic and molecular pathways that drive organ development are conserved to humans Altogether, this brings the zebrafish in a prominent position as an affordable and feasible model system to perform high throughput in vivo screens.  

1:30 - 2:00 
Collaborative Phenotyping at King's College London: HipSci and the Stem Cell Hotel
Davide Danovi, King's College London, Director, HipSci Cell Phenotyping

A clear understanding of the limitation of the current approaches in Drug Discovery is emerging throughout academia and industry. Efforts incorporating relevant cells, advanced cell culture techniques, artificial microenvironment, imaging and data analysis are moving forward allowing unprecedented opportunities in the modelling of diseases and identification of targets and therapies. The HipSci project brings together the Wellcome Trust Sanger Institute, the University of Dundee, King’s College London and the European Bioinformatics institute. A large panel of hundreds of cell lines reprogrammed from adult cells donated by healthy volunteers and patients are being fully characterised in genomics, proteomics and cell behaviour. We work within this framework at the Centre for Stem Cells and Regenerative Medicine directed by Fiona Watt at King’s College London. We have established assays for imaging of induced pluripotent stem cells and are also developing solutions to integrate dynamic and end-point high content data with the other datasets provided by the partner centres in the project. The expertise in stem cell biology, image analysis and engineered substrates as well as access to specialised equipment are now opening to interested scientists through a dedicated collaborative phenotyping space, the Stem Cell Hotel.

2:00 - 2:30 
Phenomics in the precision medicine of solid tumors
Vilja Pietiäinen, Institute for Molecular Medicine Finland FIMM

Our aim is to gain better understanding of the cancer biology and eventually to tailor drugs for patients by extensive -omics profiling of cancer patient -derived cells (PDCs) and tissues. In addition to genetic profiling of original tumor tissues, the developed PDC models are characterized with genomics, image-based phenotyping (phenomics) and high throughput drug profiling. Here, we present how these methods are applied in our precision medicine project on solid tumors, specifically renal cancer. First, the original tumor tissue and the PDCs are analyzed by exome sequencing to ensure that somatic driver mutations and copy number variations are shared between the tissue and corresponding cell models. This is followed by phenomics approach, which allows comprehensive phenotypic characterization of tissues and ex vivo cell cultures, detection of biomarkers at very early stages, and functional analysis of drug responses at the single cell level. For the image-based drug profiling, the PDCs are treated with a library of >500 oncology compounds in five different concentrations, immunostained, and subjected to automated high-content imaging and image analysis. The features extracted from single cells are used for phenotypic classification based on machine learning to provide information on drug effects on the different cellular phenotypes. In our proof-of-concept study of clear cell renal carcinoma, PI3K/mTOR pathway inhibitors were found to be among the drugs inhibiting the proliferation of renal cancer PDCs, in agreement with detected somatic mutations affecting these pathways. In addition, our image-based drug sensitivity testing revealed the intra-sample heterogeneity in drug sensitivity and resistance. We are now further investigating the mechanisms of most potent drugs and their combinations in PDCs at single cell level. As a conclusion, our results implicate the importance of genomics and phenomics in comprehensive characterization of PDCs, and how phenomics enables the scoring of drug responses in heterogenic cancer cell cultures. We foresee that these approaches may potentially improve the translation of results back to clinic and support the design of combination therapies in cancer.

Moderators
Speakers
avatar for Davide Danovi

Davide Danovi

Director, HipSci Cell Phenotyping, King's College London
Dr. Davide Danovi is leading the HipSci Cell Phenotyping group at the Centre for Stem Cells and Regenerative Medicine at King's College London in the framework of the Wellcome Trust and MRC funded HipSci project. | | Davide holds an MD from the University of Milan and a PhD in ... Read More →
ES

Emma Shanks

Head of Screening, Beatson Institute
The Screening Facility couples genetic and chemical high throughput screening with multiparametric phenotypic image analysis to support translational cancer research. We employ functional genomics (siRNA, shRNA, CRISPR) tools in both pooled and arrayed approaches to support targe... Read More →
avatar for Vilja	Pietiäinen

Vilja Pietiäinen

Senior Scientist, FIMM/University of Helsinki


Wednesday September 20, 2017 12:00pm - 2:30pm
Rosales I Courtyard by Marriot Madrid Princesa Hotel

2:30pm

Lunch Break in Exhibition
Wednesday September 20, 2017 2:30pm - 3:30pm
Rosales 2+3 Courtyard by Marriot Madrid Princesa Hotel

2:30pm

Poster Viewing in Exhibition
Wednesday September 20, 2017 2:30pm - 3:30pm
Rosales 2+3 Courtyard by Marriot Madrid Princesa Hotel

3:30pm

Exhibitor Tutorial
Wednesday September 20, 2017 3:30pm - 5:30pm
Galileo III Courtyard by Marriot Madrid Princesa Hotel

3:30pm

Exhibitor Tutorial
Wednesday September 20, 2017 3:30pm - 5:30pm
Rosales I Courtyard by Marriot Madrid Princesa Hotel
 
Thursday, September 21
 

8:30am

Registration Open
Thursday September 21, 2017 8:30am - 9:30am
Foyer Courtyard by Marriot Madrid Princesa Hotel

9:00am

SDDN Programming: Scientific Presentations
This year the SDDN / SLAS 2017 meeting has the theme "Case Studies in Drug Discovery and Development", and it will showcase several success stories, from academia, biotech, and pharma; opportunities, challenges, solutions and lessons learned will be highlighted. 

This programme is graciously sponsored by Promega

Welcome and opening remarks will be followed by three (3), 30-minute presentations

9:00-9:30 
Presentation Title Forthcoming
José Antonio Enríquez, CNIC 

9:30-10:00 
Presentation Title Forthcoming 
Miguel Vega, Allinky 

10:00-10:30
Presentation Title Forthcoming
María Jesús Vicent, Polypeptide Therapeutic Solutions 

Speakers
MJ

María Jesús Vicent

Team Leader (Polymer Therapeutics Laboratory-Scree, Centro de Investigación Príncipe Felipe


Thursday September 21, 2017 9:00am - 10:30am
Rosales I Courtyard by Marriot Madrid Princesa Hotel

10:30am

Coffee Break: Sponsored by Promega
Thursday September 21, 2017 10:30am - 11:00am
Foyer Courtyard by Marriot Madrid Princesa Hotel

11:00am

SDDN Programming: Scientific Presentations
This year the SDDN / SLAS 2017 meeting has the theme "Case Studies in Drug Discovery and Development", and it will showcase several success stories, from academia, biotech, and pharma; opportunities, challenges, solutions and lessons learned will be highlighted. 

This programme is graciously sponsored by Promega

This session will include four, 30-minute presentations. 

11:00-11:30
Presentation Title Forthcoming 
Julio Martin, GlaxoSmithKline

11:30-12:00 
Presentation Title Forthcoming 
Raul Martin, Ysios Capital 

12:00-12:30 
Presentation Title Forthcoming 
Amelia Martín Uranga, Farmaindustria 

12:30-1:00
Presentation Title Forthcoming 
Arsenio Nueda, Almirall / ASEBIO 



Thursday September 21, 2017 11:00am - 1:00pm
Rosales I Courtyard by Marriot Madrid Princesa Hotel

1:00pm

SDDN Programming: Roundtable Discussion
This year the SDDN / SLAS 2017 meeting has the theme "Case Studies in Drug Discovery and Development", and it will showcase several success stories, from academia, biotech, and pharma; opportunities, challenges, solutions and lessons learned will be highlighted. 

The morning's speakers will participate in a moderated roundtable discussion moderated by Ion Arocena, ASEBIO. 

This programme is graciously sponsored by Promega

Moderators
Speakers
MJ

María Jesús Vicent

Team Leader (Polymer Therapeutics Laboratory-Scree, Centro de Investigación Príncipe Felipe


Thursday September 21, 2017 1:00pm - 1:30pm
Rosales I Courtyard by Marriot Madrid Princesa Hotel

1:30pm

Networking Lunch: Sponsored by Promega
Thursday September 21, 2017 1:30pm - 3:00pm
Rosales 2+3 Courtyard by Marriot Madrid Princesa Hotel