Single cell omics are rapidly redefining how scientists view heterogeneous cell populations in oncology. With high-throughput single cell technologies being developed for imaging, mass spectrometry and sequencing applications, the impact on healthcare
industries is growing momentum, though this potential requires much nurturing before single cell technologies can be integrated for use with biomarkers for diagnostics and therapeutics. At Cambridge Healthtech Institute’s Inaugural Single-Cell Analysis symposium, receive updates on the latest single cell technologies to disrupt the market and compare and contrast their benefits to existing technologies.
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27 November: Single-Cell Analysis
27 November Dinner Course: SC3: The Origins, Optimization and Application of Organ-on-a-Chip Systems
28-29 November: Preclinical Models for Cancer Immunotherapy and Combinations
29-30 November: CNS Models and Translational Strategies
29 November Dinner Course: SC4: Immunology Basics for Drug Discovery, Part 2: Immune-Oncology and Autoimmunity
Tuesday 27 November
7:00 Registration and Morning Coffee
8:20 Welcome Remarks
Joel Hornby, BSc, Conference Director, Cambridge Healthtech Institute
8:25 Chairperson’s Opening Remarks
Dimitry Ofengeim, PhD, Lab Head, Neuroimmunology, Neuroscience, Sanofi
8:30 Therapeutic Approaches to the Nervous System: One Cell at a Time
Dimitry Ofengeim, PhD, Lab Head, Neuroimmunology, Neuroscience, Sanofi
Single-cell RNA sequencing (scRNA-seq) is a sequencing platform that enables the analysis of transcriptomes from individual cells and is ideally suited to address the inherent complexity and dynamics of the central nervous system. There has been recent
progress and challenges in applying scRNA-seq to advance our understanding of the brain in the application of this technology in the discovery of therapeutic targets and biomarkers for neurodegenerative diseases.
9:00 Single Cell Transcriptomic Analysis Workflow for Characterizing Complex Datasets of a Novel Human Corticogenesis Model
Marilisa Neri, PhD, Data Scientist, NIBR, Novartis
Single cell RNAseq is used to characterize a novel in vitro model of corticogenesis. Using our internally developed workflow, the neuronal differentiation has been characterized at cell granularity level: cell populations,
marker genes and phenotype heterogeneity. Novel developed method for rare/sub cell types identification, CellSIUS (Cell Subtype Identification from Upregulated gene Sets), enabled characterization of a novel protocol that recapitulates the full spectrum
of cortical development, including upper-layer corticogenesis in vitro.
9:30 Spatial Transcriptomics - Bridging Histology and RNA Sequencing
Michaela Asp, PhD, Department of Gene Technology, Science for Life Laboratory, Royal Institute of Technology
Spatially resolved transcriptomics provides us with new insights into the molecular diversity of heterogeneous tissue structures. Several approaches have been established in order to preserve gene expression information together with its tissue localization.
However, existing challenges for many spatial technologies include the extent of existing knowledge about the targets, the labor-intensive nature of the methods or the fact that they are not applicable to clinical samples. Here, we present a method
whereby whole intact tissue sections can be studied in a spatial whole-transcriptome manner.
10:00 Coffee Break
10:30 The Impact of Cell Proliferation and Microenvironment on Tumour Heterogeneity
Anders Ståhlberg, PhD, Associate Professor, Clinical Pathology and Genetics & Sahlgrenska Cancer Center, University of Gothenburg & Sahlgrenska University Hospital
Here, we will show how cell proliferation and cancer stem cell properties contribute to intratumor heterogeneity in two entities: breast cancer and liposarcoma. We will also describe how the microenvironment determines the cellular phenotype of individual
cells. To outline cell fate mechanisms we employed various single-cell techniques and functional assays.
11:00 Subcellular Spatial Analysis of Transcriptome and Proteome during Early Development
Radek Sindelka, PhD, Senior Scientist, Department of Gene Expression,
Institute of Biotechnology, Czech Academy of Sciences, BIOCEV
Starting from a single fertilized oocyte, through manifold of divisions a complex organism is developed that has distinct asymmetries. One of the main challenges in developmental biology is to understand how and when these asymmetries are generated and
how they are controlled. The African clawed frog (Xenopus laevis) is an ideal model for studies of early development thanks to their very large oocytes. We have developed a unique platform based on RT-qPCR, RNA-Seq and UPLC-ESI-MS/MS to measure asymmetric
localization of fate determining RNAs and proteins within the egg and among the early stage blastomeres.
11:30 Enjoy Lunch on Your Own
13:25 Chairperson’s Remarks
Dimitry Ofengeim, PhD, Lab Head, Neuroimmunology, Neuroscience, Sanofi
13:30 The Future of Pre-Implantation Genetic Testing - Accurate and Non-Invasive
Xiaoliang
Sunney Xie, PhD, Lee Shau-kee Professor and Director of the Beijing Innovation Center for Genomics at Peking University, and Harvard University Visiting Professor, Biodynamic Optical Imaging Center, Peking University
Single-cell whole-genome amplification is critical for IVF. Current whole-genome amplification (WGA) methods present low accuracy of copy-number variation (CNV) and low amplification fidelity. We developed MALBAC and LIANTI, achieving the highest precision
for single-cell genome sequencing with quasi linear and linear amplification, respectively, as opposed to exponential amplification in PCR. Based on these, we developed MARSALA, NICS and MaReCs, to successfully select fertilized eggs free of chromosome
abnormalities and devastating point mutations in more than 300 couples.
14:00 Metabolic Imaging of Single Cells Using Mass Spectrometry
Greg McMahon, PhD, Principal Research Scientist, NanoSIMS Imaging, National Centre of Excellence, Mass Spectrometry Imaging, National Physical Laboratory (NPL)
Recent major advances in mass spectrometry imaging are now enabling drug uptake and metabolic heterogeneity to be studied at the single-cell scale. This includes the 3DOrbiSIMS (Passarelli et al, Nature Methods, 14, 1175 (2017)) using a focused ion beam
to image the surface and AP-MALDI (Kompauer, Nature Methods, 14, 90 (2017)) where an axial focused laser beam is used. These methods provide complementary metabolomic information and will be placed in context with other single-cell omics methods.
14:30 Single Cell Mass Spectrometry in the Context of Drug Discovery
Carla Newman, Investigator, Ex vivo Bioimaging, GlaxoSmithKline
A paradigm shift in the drug discovery workflow is required to reduce attrition and transform conventional drug screening assays into translatable analytical techniques for the analysis of drugs in complex environments, both in vitro and ex vivo. We propose the use of two mass spectrometry techniques: SIMS and static electrospray mass spectrometry to visualise unlabelled compounds inside the cell at physiological dosages that can offer valuable
insight into the compound behaviour both on and off-target.
15:00 Refreshment Break
15:30 Single Cell Antibiograms
Piotr Garstecki, PhD, Professor, Microfluidics and Complex
Fluids, Institute of Physical Chemistry, Polish Academy of Sciences
Droplet microfluidics is an ideally suited technology for digital assays for bacterial cell counting and offers the possibility to probe the response of bacteria to antibiotics at the single cell level. The technology offers several interesting
features – including alleviation of the unwanted inoculum effect in antibiogram assays and information on the distribution of susceptibility in the population.
16:00 Decoding Neuronal Diversity by Single Cell Convert-Seq
Joachim Luginbuehl, PhD, JSPS Fellow, RIKEN Yokohama
We present Convert-seq, combining single-cell RNA sequencing (scRNA-seq) and pooled (mutiplexed) ectopic gene expression with a new strategy to discriminate sequencing reads derived from exogenous and endogenous transcripts. We demonstrate Convert-seq
by associating hundreds of single cells at multiple time-points during direct conversion of human fibroblasts to induced neurons (iN) with exogenous and endogenous transcriptional signatures. Convert-seq is a broadly applicable workflow to
rapidly identify key transcription factors orchestrating the direct conversion of virtually any cell type.
16:30 Droplet Microfluidics for High Throughput Biopharmaceuticals Screening
Håkan Jönsson, PhD, Assistant Professor, KTH Royal Institute of Technology
Biopharmaceuticals make up the majority of highest grossing drugs. Many protein therapeutics are produced in mammalian cell factories such as CHO or HEK293. Droplet microfluidics allows for single cell level high-throughput analysis of protein
secretion. We present a platform based on split-GFP complementation in droplets, which enables screening of a heterogeneous variant library, transfectant pool enrichment by protein secretion and selection of a highly productive clone.
17:00 Close of Symposium
18:00 – 20:30 Recommended Dinner Short Course*
SC3: The Origins, Optimization and Application of Organ-on-a-Chip Systems
* Separate registration required.