ESR 7: uHeart: an in vitro human miniaturized model for the detection of drug-induced functional cardiotoxicity.

 

 

ESR7

Project Title: uHeart: an in vitro human miniaturized model for the detection of drug-induced functional cardiotoxicity.

Objectives: The ESR will be trained in the development of organ-on-chip platforms. In particular, the ESR will develop an advanced miniaturized 3D model of human beating heart (uHeart), integrated with capabilities for extracting action potential measurements and assessing drug effects on contractility. uHeart will be fully validated and the effect of drugs known to induce alterations in the action potential (i.e. QT wave prolongation) will be extracted from the platform, to demonstrate the potential of uHeart to detect cardiac toxicity better than current bidimensional and single-cells standard tests. This approach will i) guarantee the achievement of a mature model of human beating cardiac tissue, ii) allow for extrapolation of relevant cardiac electrical response (i.e. QT length), and iii) ensure a level of throughput compatible with drug screening applications. The ESR will adopt engineering design tools (CAD, FEM), state-of-the-art microfabrication techniques and iPSC technology.

Expected Results: An innovative microscaled platform will be developed, recapitulating a human fully functional cardiac tissue within a chip. The platform will be integrated with a reading system able to extrapolate action potentials. It is anticipated that development of this technology will offer a versatile and high-throughput platform to assess in vitro the functional cardiotoxicity induced by drugs directly on a human model. The first prototype, released at month 24, will indeed undergo a pharmacological validation as predictor of drug cardiotoxicity, and will eventually be refined according to validation outcomes.

Host: BIOMIMX

Main Supervisors: Paola Occhetta (BIOMIMX), Roberta Visone (BIOMIMX)

Duration: 36 months

Expected start date: 1 February 2020

Planned Secondment: ICRC Brno (3 months) during the first year and a half to acquire knowledge in iPSC production and differentiation in cardiomyocytes; POLIMI (2 months) during the second year to design the microfluidic device; MTTLAB (2 months) during the last year to define and run a pharmacological validation strategy in line with the requirements for a new in vitro model to enter the drug discovery pipeline.

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

Profile: An ideal ESR candidate will hold a Master’s degree and has excellent marks from his/her previous studies and courses along with experience in one or more of the relevant fields. Excellent written and oral communication skills in English and attitude to work in a team are a must.

Furthermore, the candidate has/is:

  • A MSC degree in Biology, Biotechnology, Biomedical Engineering, Technical Biology or equivalent title
  • Enthusiastic about pursuing an interdisciplinary research project within a fast-growing startup
  • Knowledge and experience in working with three-dimensional and possibly miniaturized in vitro culture system
  • Knowledge and experience in the cardiac field and/or toxicology

For any specific requests on this project, please get in contact with Dr. Paola Occhetta (paola.occhetta@biomimx.com)