Raphael Volpert

Objective

Measure the effect of experimental nootropics such as PRL-8-53, Idra-21 and Lion's Mane on human cognitive performance using brain organoids.

Creating the first standardized neurochemical benchmark for cognitive enhancers "Nootropic-Analysis".

Discover the optimal blueprint of compounds to decrease tolerance buildup and volatility from baseline while still enhancing cognition.

Motivation

Progress in discovering compounds which enhance brain health and performance has been held back by two bottlenecks:

• Limited functional neuroimaging, both metabolic and electrical, and fMRI, is not a good marker for the neurochemical effects of compounds.
• The slow turnaround of rodent and primate studies.

Building an automated brain organoid facility removes both barriers:

• Because the tissue is exposed rather than encased, we can directly couple it to microscopes, multi-electrode arrays, optical reporters, and metabolic assays.
• Scale of labautomation: allowing to run hundreds of "drug discovery-runs" instead of needing to do manual liquid handling, optical readout and data analysis for just a single one.

Milestones

In the first 3 months of Calculus, I am developing an open-source and highly modular version of the Cortical Labs CL1, focusing on the two hardest parts: the perfusion system and microelectrode array.

After setting up the infrastructure, I will start my first "Benchmarking-Run" on the Lion's Mane compound and measure the ability of the organoids to solve problems.

• Record baseline electrophysiology with multi-electrode arrays, track calcium dynamics, and capture transcriptomic profiles.
• Monitor changes in synaptic-plasticity markers (BDNF, phosphorylated CREB), histone acetylation levels, and network oscillations linked to memory.