ESR 15: Development of a patient-specific a lab-on-chip cardiac microtissue model of dystrophin deficient cardiomyopathy.

 

 


ESR15

Project Title: Development of a patient-specific a lab-on-chip cardiac microtissue model of dystrophin deficient cardiomyopathy.

Objectives: The aim of the project resides in exploiting iPSCs banked at the Partner Organisation (MONZINO) derived from healthy patients and patients affected by Duchenne’s and Becker’s Muscular Dystrophy (DMD/BMD respectively) a genetic disorder with common involvement of heart muscle complications (e.g. dilated cardiomyopathy complicated by arrhythmias) or other forms of cardiomyopathy. These cell sources will allow the development of an innovative approach for modelling the disease in a patient-specific fashion and in a high-precision microphysiological system (MPS) aimed at outperforming current in vitro standards. The final model is expected to allow drug screening and functional on-chip readings such as innovative cardiac microtissues action potential measurements, functional contractility assays and more traditional assays such as immunofluorescence and RT-PCR.

Expected Results: An innovative LoC device meant for culturing, training and analysing patient-specific cardiac microtissues. A novel biological model representing a milestone in precision medicine (MPS), allowing for the first time disease modelling and relevant functional readouts that truly improve the faithfulness to cardiac physiology and thus the reliability of tests. A pharmacological validation with potential therapeutic strategies (e.g. identification of drug-induced electrophysiological alterations; dose-response curves of functional parameters such as contractility and force production).

Host: POLIMI

Main Supervisors: Marco Rasponi (POLIMI), Aoife Gowran (MONZINO)

Duration: 36 months

Expected start date: 1 May 2020

Planned Secondment: MONZINO (6 months) in the first year to learn about iPSC culture protocols, while in the second&third years she/he will also participate in cell culture lab activities at MONZINO; ICRC Brno (2 months) during the second year to acquire knowledge on advanced assays for cardiac functionalities at FNUSA (e.g. live imaging of calcium dynamics).

Enrolment in Doctoral Degree: PhD in Bioengineering at Politecnico di Milano


For any specific requests on this project, please get in contact with Prof. Marco Rasponi (marco.rasponi@polimi.it)