Background

Reliable production of soluble and stable proteins is central to agricultural biotechnology, supporting improved crop traits, biocatalysts, diagnostics and biological solutions. Yet protein-expression performance depends strongly on construct design and host-cell context, and conventional screening approaches often lack the throughput needed to investigate large variant libraries.

This project will develop droplet-based microfluidic approaches to screen genetically diverse Escherichia coli expression variants. Individual cells will be compartmentalised in nanolitre droplets and assessed through fluorescence-based readouts. The aim is to establish scalable screening workflows for identifying genetic constructs that promote robust protein production.

This 3-month internship or 6-month thesis project will be based in the laboratory of Professor Andrew deMello at ETH Zürich, in collaboration with Syngenta Crop Protection AG. Experimental activities may also be supported at the Syngenta Research Center in Stein, AG.

Objectives

• Develop a workflow for encapsulating individual E. coli cells carrying protein-expression variants in nanolitre droplets.

• Establish conditions supporting cell viability, growth and protein expression in droplets.

• Implement fluorescence-based assays to measure protein expression.

• Assess compatibility with fluorescence-activated droplet sorting.

• Screen genetic construct libraries and compare expression levels, growth and assay reproducibility.

Duration: 3-6 months

Background

Filamentous fungi are important producers of natural products, bioactive compounds and biocatalysts. Their use in droplet-based microfluidic screening is nevertheless limited because growing hyphae can penetrate conventional water-in-oil droplets, compromise their integrity and escape the compartment.

This project builds on previous work on fungal microreactors and aims to develop robust core–shell beads for the confinement of genetically diverse fungal populations. Different hydrogel and polymer shell materials will be tested to identify formats that support fungal growth while preventing hyphal penetration and loss of containment. The longer-term goal is to enable ultra-high-throughput screening for fungal strains with improved natural-product production.

This 3-month internship or 6-month thesis project will be based in the laboratory of Professor Andrew deMello at ETH Zürich, in collaboration with Syngenta Crop Protection AG. Experimental activities may also be supported at the Syngenta Research Center in Stein, AG.

Objectives

• Develop droplet-microfluidic methods to generate core–shell microreactors for filamentous fungi.

• Evaluate different hydrogels and biocompatible polymers as shell-forming materials.

• Assess fungal viability, growth, confinement and hyphal penetration for each microreactor format.

• Compare candidate beads for reproducibility, mechanical stability and compatibility with downstream screening.

• Evaluate fungal release and re-growth after a selection stage.

• Explore integration of metabolite or small-molecule detection for downstream analysis. (Optional.)

Duration: 3-6 months

Our group recently developed a paper-based electrochemical assay for monitoring creatinine in urine. This test was able to detect creatinine within physiologically relevant levels, and in the presence of common contaminants. In  this project, we want to integrate this assay into a fully integrated prototype device, and also expand its capabilities  to detect proteinuria. We will achieve this through the following objectives.  

1) Develop and optimize a paper-based electrofluidic assay for both creatinine and proteinuria

2) Integrate these optimized assays into a prototype 3D-printed device 

3) Evaluate the performance of the device on patient samples obtained from Unispital Zürich.

The aim of this project is to apply our new SGC technology toward the detection of Mycobacterium tuberculosis (MTB), particularly drug-resistant forms. During the project, we will design new SGCs for several target genes indicative of MTB and rifampicin-resistant MTB infections. We will then integrate these SGCs into a colourimetric paper-based device, with the ultimate aim of creating a highly accessible diagnostic device.  The work will be split into three aims. 

1) Design and synthesise SGCs specific to gene targets for MTB and rifampicin-resistant MTB

2) Integrate these SGCS into colourimetric assays that can be interpreted by humans / smartphone cameras 

3) Transfer these assays onto a custom-built paper-based test strip / 3D printed housing

This project aims to identify potential functional mRNAs from an established mRNA library that can significantly improve the efficacy of immune cell therapy. Utilizing a droplet microfluidics platform, we provide thousands of mRNAs with independent environments for concurrent screening.

Candidate Requirements:

Strong background in biology

Basic knowledge of engineering principles

If you are Interested, please send your CV and motivation letter to:

Rashin Mohammadi (rashin.mohammadi@chem.ethz.ch)

Junyue Chen (chen.junyue@chem.ethz.ch)

Join us in advancing immunotherapy through cutting-edge mRNA screening technology!