Automation, engineering and computational biology: My Year in Industry

With an aim to pursue a career in research and wanting to gain hands-on experience with the technical and professional skills required, I applied to the Earlham Institute’s Year in Industry programme and was fortunate enough to be accepted. 

Once I’d arrived at Earlham, I spent my first few weeks meeting with different research groups to discuss potential projects. I wanted to engage as much as I could with the wide diversity of research taking place at the institute, which made the interdisciplinary project I selected an exciting opportunity to gain a diverse set of skills and experiences. 

This project is a collaboration between two research groups focusing on seemingly very different fields of biology. 

One is the Haerty Group, led by Dr Wilfried Haerty, specialising in computational genomics, while the other is the Earlham Biofoundry led by Dr Carolina Grandellis which specialises in synthetic biology and cutting-edge automation. 

The project itself employs a blend of the Haerty Group’s computational expertise with the Biofoundry’s capacity for automation and bioengineering to advance both research areas. 

The Earlham Biofoundry is one of a handful of biofoundries in the UK and represents a powerful resource for molecular biology research. The Biofoundry houses many state-of-the-art machines for automation, allowing it to undertake large scale experiments outside the scope of most labs. 

As an undergraduate student, working in such a high-tech environment has been an amazing, if slightly surreal, experience. Being surrounded by all the futuristic machines in the lab can feel like something out of the set of a sci-fi film. One of these machines is the Echo 650, an acoustic liquid handler which uses soundwaves to shoot tiny volumes of liquid, down to 2.5 nanolitres, between plates - bypassing the need for pipetting. This machine is the backbone of my project, the long-term aim of which is to develop a high throughput, species agnostic method for validating protein-protein interactions (PPIs). 

PPIs are a fundamental aspect of molecular biology, making their identification and characterisation vital for understanding and engineering biological systems. Predictive AI models such as AlphaFold have been widely adopted for predicting which proteins may engage in PPIs, though their lack of benchmarking can call the reliability of their outputs into question. Our pipeline could have the capacity to validate these predictions, opening the potential to accelerate a range of research areas in molecular biology, from novel drug discovery to developing disease-resistant plants. 

The Echo is instrumental to developing this pipeline by scaling up the commonly used Yeast Two-Hybrid method of PPI screening. After transforming yeast strains with two potentially interacting proteins, I use the Echo to transfer tiny volumes of the yeast cultures to trays filled with selective growth media, where reporting of PPIs could be visualised. 

This semi-automated method allows for up to 384 individual strains to be grown on the same tray, while the transfer itself takes no more than 5 minutes. This is much faster than manual pipetting with a lower chance for error, no requirement for plastic pipette tips and the capacity for miniaturisation as the volumes transferred can be minute. 

Experiencing first-hand the Echo’s capabilities for aiding advanced, high-throughput experiments has been really inspiring; working in the Biofoundry has been an incredible opportunity to delve into the rapidly developing field of engineering biology. 

For example, earlier this year I had the opportunity to teach visiting researchers how to use the Echo for experiments at our Automation and Engineering Biology for Plant & Microbial Systems workshop. Chatting with and tutoring the range of visitors from academia and industry, with research ranging from human health to sustainable agriculture, signified to me just how much can be gained from implementing engineering biology and automation into different fields of study.  

Outside of the Earlham Biofoundry, I’ve been working in the computationally-focused Haerty Group, combining my work in the lab with genomic analysis to further our understanding of alternative splicing. 

Alternative spicing is a fundamental process during the protein synthesis of eukaryotic organisms, in which multiple different protein-coding transcripts can be produced from a single gene, generating a huge diversity of protein isoforms from a comparatively small set of genes.

The importance of alternative splicing to biological systems is demonstrated by its dysregulation. In the human brain and nervous system, alterations to splicing patterns can result in neuropsychiatric conditions like schizophrenia and bipolar disorder. Understanding the processes and consequences of alternative splicing is critical to uncovering new therapeutic methods for these conditions. 

Our PPI-validation pipeline can be a useful tool for advancing this understanding. Genomic analysis of long-read RNAseq datasets, extracted from human brain and nervous system tissues, can identify pairs of alternatively spliced protein isoforms that could potentially be interacting with one-another to form complexes. By taking this isoform list and testing the protein-pairs in the PPI-screening pipeline we’ve been developing in the Biofoundry, we can validate whether these pairs are truly complex-forming. 

These results have the potential to advance our understanding of the functional consequences of alternative splicing and may aid in the discovery of novel therapeutic targets.

Whilst working on the dry lab side of this project, I’ve been practicing carrying out genomic analysis which has been extremely useful to learn alongside my work in the lab. Having such an interdisciplinary project has been a valuable opportunity to gain a diverse set of skills and to learn about the importance of collaboration between different scientific disciplines. 

Working with state-of-the-art machines in the Biofoundry and advanced computational techniques using the High-Performance Computing infrastructure are experiences you can only really get with a placement like this. Though the Haerty and Biofoundry Group's may at first seem worlds apart, combining their expertise in this project is leading to advancements in both the Haerty group’s research into understanding transcript regulation, as well as the Biofoundry’s development of advanced synthetic biology techniques. 

At university, it can sometimes feel like there’s a wall between different scientific disciplines, so working between these two groups has really illuminated what makes cross-disciplinary research so important. 

Through building my confidence in planning and conducting experiments and providing opportunities to engage with the wider scientific community, my time at the Earlham institute has confirmed my passion for research and interest in engineering biology. I’d recommend the Year in Industry programme to anyone considering a future in research. As for me, I’m looking forward to pursuing a PhD and beyond in the future, whilst carrying the knowledge that collaboration is the key to delivering important and exciting science.