Team:UniGE-Geneva

Unige iGEM 2019

Fluosphera

Project

Current in vitro drug-discovery often misses prodrugs and selects compounds with adverse side effects. Indeed, inter-tissue communication is not recapitulated by simple cell culture methods, allowing the progression of suboptimal compounds during drug development.

1 Drug Discovery Today

Drug discovery is a resource intensive process that typically involves screening thousands of different molecules on in vitro cell cultures to find drug candidate 'hits' with desirable effects. The 'hits' are then optimized by chemistry, extensively evaluated for a wide range of biochemical and biological properties including toxicity, and tested in small animal models of the disease or condition of interest, before progressing to human clinical trials if all previous tests results appear favourable.

Inspiration

2 Current Screening Model

One of the crucial steps of pharmacological drug testing approaches is the evaluation of cellular activities using either conventional 2D or 3D cultures. These models have limitations that have resulted in high attrition rates during drug discovery.

3 What about Physiological Communication?

The different tissues of the human body are all physiologically interconnected because sophisticated biochemical and signalling pathways coordinate the functioning of different organs. Many current 3D spheroid drug testing protocols use single types of cells, which does not capture the inter-tissue communication of whole organisms.

4 A Step forward: 3D Cell Co-Culture

3D cell culture generates multicellular structures called spheroids to recapitulate part of the spatial organization of tissues. Mixing spheroids that are comprised of different types of cells may increase the physiological relevance and of in vitro drug testing methods. However, each type of spheroid needs to be individually evaluated in order generate meaningful results.

Solution!

5 A breakthrough with cell encapsulation

Spheroids from different tissues are encapsulated in permeable fluorescent capsules allowing them to communicate in the same well while making their recognition easy using a fluorescent microscope. This way we create a system where customers can simultaneously monitor the phenotypic output of different cell types in a single well. Co-culturing different cell types together is intended to increase the biological relevance of the system as well as provide more information concerning the toxicity of a compound for multiple cell types in the same well.

6 Tracking Multiple Biological Activities

Spheroids can be prepared with genetically-engineered cells to monitor several biological activities, including toxicity, anti-cancer effects, etc., via the use of fluorescent reporters. This allows the creation of a wide range of "cell type - reporter" combinations, resulting in high-content drug testing systems designed to meet the needs of therapy developers who see the value of multiplexed screening approaches.

Fluosphera: next-generation cell culture

7 High-content in vivo-like possibilities

Multiplexed multi-organ (in vivo recapitulating) cell culture: fluorescent microscope imaging of labeled-capsules and cell spheroid reporter genes can simultaneously quantitate multiple biological activities in different cell types.

Fluosphera in action.

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High Content Screening

8

We are pleased to present our advance in the drug discovery process that significantly improves the physiological relevance of in vitro cell cultures, while maintaining wide applicability and high-throughput capacity.