Multi-omics analysis of the brain at single cell resolution

14:40 - 16:00 BST | Thursday 15th April 2021

Faculty

Co-chairs:

  • Johanna Jackson, UK Dementia Research Institute at Imperial, UK ( co-chair)
  • Carlo Sala Frigerio, UK Dementia Research Institute at UCL, UK (co-chair)

Speakers:

  • Carlo Sala Frigerio, UK Dementia Research Institute at UCL, UK (co-chair) - Pushing the boundaries of multi-omics brain analysis (workshop introduction)
  • Viola Volpato, UK Dementia Research Institute at Cardiff, UK - A deep single cell atlas of the human substantia nigra to study Parkinson's Disease progression​
  • Sarah Marzi, UK Dementia Research Institute at Imperial, UK - Epigenetic regulation in neurodegenerative disease​
  • Jo Anne Stratton, McGill University, Montreal, Canada- Single cell profiling of ependymal cells
  • Seth Grant, University of Edinburgh, UK - Synapse proteome complexity and the architecture of synapse diversity​
  • Kenneth Harris, University College London, UK - Identifying fine cellular subtypes in situ with multiplexed in situ RNA sequencing

Description

The single-cell “-omics” revolution, nominated Method of the year 2019 by the journal Nature Methods, has impacted the world of research like few other technological advancements.

The molecular study of the brain is complicated by the very nature of the brain tissue, where cells cannot be readily dissociated and therefore measurements have been historically averaged across multiple cell types.Techniques allowing the analysis of different types of biomolecules (DNA, RNA, protein, lipids) offer the possibility of gaining a comprehensive molecular view of the brain, obtained by amalgamating the different “-omics” layers.  

Thus the availability of techniques probing multiple “-omics” layers at single-cell resolution is paving the way to disentangle brain biology and to understand the contribution of individual cell types to brain pathology.  Data obtained through single-cell resolved techniques can be further used to deconvolute “bulk” datasets, which average the contribution of different cell types present in a tissue sample, thus increasing the depth of analysis. Thanks to the synergy of single-cell and bulk multi-omics techniques, we have a more detailed insight into brain biology.

Being able to draw comparison between multiple dimensions of a cell state (gene expression, protein expression, membrane composition and synaptic proteomic composition) has important implications for understanding disease manifestation and progression and identifying new drug targets.

Aims of the workshop

In this workshop, we will discuss how recent single-cell and bulk multi-omic techniques are being used to push the boundaries of our knowledge of brain physiology and brain diseases.

The workshop will cover topics including transcriptomics, proteomics, lipidomics, computational biology, and novel spatial-resolved techniques which allow the analysis of biomolecules directly in situ on a tissue section, including technical and computational challenges and opportunities. 

Recommended reading

To get the most out of this workshop the organisers have prepared this wonderful list of resources for you to look at before (and after) the actual session.

Resources for single cell analysis of dementia and neurodegeneration

Recent publications:

Resources for single cell expression quantitative trait loci (eQTL) analysis and transcriptome-wide association studies (TWAS)

Recent publications:

Software tool:

Resources for spatial transcriptomics

Recent reviews:

Recent experimental papers:

Resources for synapse analysis

Recent publications:

The mouse lifespan synaptome atlas:

Podcast:

Video:

 

 

This workshop is convened by the UK Dementia Research Institute