Agniesz­ka Krzyżosiak

Title

HE Twin­ning — SAME-Neu­roID — Stan­dard­ized approach­es to mod­el­ling and exam­i­na­tion of neu­ropsy­chi­atric disorders

Abstract

Hori­zon Europe Widen­ing pro­grams such as Twin­ning and Team­ing for Excel­lence enable the devel­op­ment of mod­ern, effi­cient research insti­tu­tions in Poland through the trans­fer of best prac­tices in research man­age­ment, tech­nol­o­gy trans­fer and edu­ca­tion from more advanced Euro­pean part­ners. This PORT objec­tive of SAME-Neu­roID Twin­ning was active­ly sup­port­ed by our part­ners in the field of neu­ro­science: Paris Brain Insti­tute (ICM, France), Max Planck Insti­tute of Psy­chi­a­try (MPI, Ger­many) and Eras­mus Med­ical Cen­ter (EMC, Nether­lands). The sci­en­tif­ic focus of this ini­tia­tive is based on the shared vision of the con­sor­tium part­ners to devel­op stan­dard­ized inter­lab­o­ra­to­ry approach­es to the mod­el­ing of neu­ropsy­chi­atric diseases.

We have devel­oped an advanced in vit­ro plat­form pro­vid­ing a coher­ent work­flow for repro­ducible and robust mod­el­ling of neu­ropsy­chi­atric traits. Build­ing on the exper­tise of our part­ners from EMC (Rot­ter­dam) and ICM (Paris), we estab­lished a state-of-the-art set of mod­els that unique­ly reca­pit­u­lates the genet­ic envi­ron­ment of the human brain in a dish. Our assays include iPSC-derived 2D cul­tures of neu­rons and glial cells as well as inno­v­a­tive iPSC-based 3D brain organoids with the advan­tage of self-orga­ni­za­tion and for­ma­tion of advanced brain-like structures.

The col­lab­o­ra­tion between MPI Psy­chi­a­try (Munich) and PORT focused on afford­able set­up for auto­mat­ed mea­sures of com­plex behav­ior in mice. The twin sys­tem has been estab­lished and val­i­dat­ed in both lab­o­ra­to­ries, along with ana­lyt­i­cal pipeline. The hard­ware fea­tures the rec­tan­gu­lar are­na, a cam­era, and a light sources enabling video record­ing under white and red light con­di­tion, to enable mon­i­tor­ing active and inac­tive phas­es of the day. The ana­lyt­i­cal work­flow is based on AI-sup­port­ed soft­ware for reli­able track­ing of indi­vid­ual ani­mals (DeepLab­Cut, SLEAP​.ai), and inter­pre­ta­tion of behav­ioral traits based on pose esti­ma­tion (deep­OF). Coher­ent data obtained from the two labs pro­vid­ed the res­o­lu­tion of behav­ioral changes elicit­ed by chron­ic social defeat stress with unprece­dent­ed detail.

The SAME-Neu­roID plat­form pro­vides a pow­er­ful tool­box for study­ing brain func­tion under both phys­i­o­log­i­cal and patho­log­i­cal con­di­tions and serves as a foun­da­tion for future trans­la­tion­al research in men­tal health disorders.

Biog­ra­phy

Agniesz­ka com­plet­ed her PhD research at The Insti­tute of Genet­ics and Mol­e­c­u­lar and Cel­lu­lar Biol­o­gy (IGBMC) in Stras­bourg, France. She next accom­plished the EMBO and HFSP fund­ed post­doc at the Med­ical Research Coun­cil Lab­o­ra­to­ry of Mol­e­c­u­lar Biol­o­gy (MRC LMB) in Cam­bridge, UK fol­lowed by the trans­la­tion­al devel­op­ment of her sci­en­tif­ic research in a spin­off biotech startup.

Agnieszka’s lab is inter­est­ed to under­stand how pro­tein qual­i­ty con­trol (PQC) dereg­u­la­tion con­tributes to neu­rode­gen­er­a­tion. In her pre­vi­ous research, togeth­er with her col­leagues, Agniesz­ka showed that PQC can be tar­get­ed for the ther­a­peu­tic ben­e­fit against pro­tein accu­mu­la­tion – an approach cur­rent­ly devel­oped clin­i­cal­ly. Build­ing on that, with the use of patient-derived mod­els, the aim of the lab is to scru­ti­nize the PQC path­ways in neu­rode­gen­er­a­tion in the aim to iden­ti­fy nov­el treat­ment strategies.