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Great ape organoids to reconstruct uniquely human development

Objective

Humans diverged from our closest living relatives, chimpanzees and other great apes, 6-10 million years ago. Since this divergence, our ancestors acquired genetic changes that enhanced cognition, altered metabolism, and endowed our species with an adaptive capacity to colonize the entire planet and reshape the biosphere. Through genome comparisons between modern humans, Neandertals, chimpanzees and other apes we have identified genetic changes that likely contribute to innovations in human metabolic and cognitive physiology. However, it has been difficult to assess the functional effects of these genetic changes due to the lack of cell culture systems that recapitulate great ape organ complexity. Human and chimpanzee pluripotent stem cells (PSCs) can self-organize into three-dimensional (3D) tissues that recapitulate the morphology, function, and genetic programs controlling organ development. Our vision is to use organoids to study the changes that set modern humans apart from our closest evolutionary relatives as well as all other organisms on the planet. In ANTHROPOID we will generate a great ape developmental cell atlas using cortex, liver, and small intestine organoids. We will use single-cell transcriptomics and chromatin accessibility to identify cell type-specific features of transcriptome divergence at cellular resolution. We will dissect enhancer evolution using single-cell genomic screens and ancestralize human cells to resurrect pre-human cellular phenotypes. ANTHROPOID utilizes quantitative and state-of-the-art methods to explore exciting high-risk questions at multiple branches of the modern human lineage. This project is a ground breaking starting point to replay evolution and tackle the ancient question of what makes us uniquely human?

Field of science

  • /natural sciences/biological sciences/genetics and heredity/genome
  • /natural sciences/physical sciences/astronomy/planetary science/planets
  • /natural sciences/biological sciences/zoology/mammalogy/primatology
  • /social sciences/other social sciences/social sciences interdisciplinary/sustainable development
  • /medical and health sciences/medical biotechnology/cells technologies/stem cells

Call for proposal

ERC-2018-STG
See other projects for this call

Funding Scheme

ERC-STG - Starting Grant

Host institution

INSTITUT FUR MOLEKULARE UND KLINISCHE OPHTHALMOLOGIE BASEL
Address
C/o Universitätsspital Basel, Augenklinik, Mittlere Strasse
4056 Basel
Switzerland
Activity type
Research Organisations
EU contribution
€ 1 500 000

Beneficiaries (1)

INSTITUT FUR MOLEKULARE UND KLINISCHE OPHTHALMOLOGIE BASEL
Switzerland
EU contribution
€ 1 500 000
Address
C/o Universitätsspital Basel, Augenklinik, Mittlere Strasse
4056 Basel
Activity type
Research Organisations