Objective Humans are endowed with a number of advanced cognitive abilities not seen in other species. So what allows the human brain to stand out from the rest in these capabilities? In general, the brains of primates, including humans, have more neurons per unit volume than other mammals. But humans are also in the fortunate position of having the largest of the primate brains, making the number of neurons in the human cerebral cortex greatly expanded. Thus, the difference seems to be a matter of quantity, not quality. My laboratory is interested in understanding how neuron number, and thus brain size, is determined in human brain development. The research proposed here is aimed at taking an evolutionary approach to this question and comparing brain development in an in vitro 3D model system, cerebral organoids. This method, which relies on self-organization from differentiating pluripotent stem cells, recapitulates remarkably well the endogenous developmental program of the human brain. Having previously established the brain organoid approach, and more recently improved upon it with the application of bioengineering, my laboratory is in a unique position to carry out functional studies of human brain development. I propose to use this approach to compare developing human brain tissue to that of other hominid species and tease apart unique features of human neural stem cells and progenitors that allow them to generate more neurons and therefore a greater cerebral cortical size. Furthermore, we will perform transcriptomic and functional screening to identify factors underlying this expansion, followed by careful genetic substitution to test the contributions of putative evolutionary changes. In this way, we will functionally test putative human evolutionary changes in a manner not previously possible. Fields of science natural sciencesbiological scienceszoologymammalogyprimatologynatural sciencesbiological sciencesevolutionary biology Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2017-STG - ERC Starting Grant Call for proposal ERC-2017-STG See other projects for this call Funding Scheme ERC-STG - Starting Grant Host institution UNITED KINGDOM RESEARCH AND INNOVATION Net EU contribution € 1 444 911,00 Address POLARIS HOUSE NORTH STAR AVENUE SN2 1FL Swindon United Kingdom See on map Region South West (England) Gloucestershire, Wiltshire and Bristol/Bath area Swindon Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 444 911,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all UNITED KINGDOM RESEARCH AND INNOVATION United Kingdom Net EU contribution € 1 444 911,00 Address POLARIS HOUSE NORTH STAR AVENUE SN2 1FL Swindon See on map Region South West (England) Gloucestershire, Wiltshire and Bristol/Bath area Swindon Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 444 911,00