Insights from a Strain Engineer: Pioneering Gene Editing and AI in Startups

Lexin Ann Morales     

Lexin Morales is the Marketing Lead of Gravel, an ingredient data intelligence platform based in London, UK. Gravel features an article series about strain engineers and fermentation engineers in the biotech industry for aspiring, young graduates wanting to become strain engineers in biotech startups.

Lexin recently spoke to Jason Shu Lim Yu, Algae Strain Engineer - at Phycoworks, where his role revolves around gene editing, algae, microbiology, and biotechnology. As a Strain Engineer in a start-up, Jason shared his experience in establishing the modular cloning and gene editing platform in the context of microalgae at Phycoworks.

Strain engineering and gene editing in Startups

Working in a start-up involves many challenges and triumphant moments. However, within this ever-evolving landscape lies abundant opportunities for both personal and professional growth. Team members in startups frequently find themselves assuming a multitude of roles, stretching their skill sets and are often pivotal in shaping the company's growth trajectory. I spoke with Jason, an Algae Strain Engineer who established the gene editing and modular cloning pipeline in microalgae at Phycoworks. He shared an overview of his role and some important insights about the significance of communication and adaptability in a start-up venture.

What is gene editing, and how is it related to your role?

As a strain engineer, we are interested in using gene editing technologies to manipulate the genetic makeup of organisms and confer novel functionalities that can be exploited economically. The primary aim of gene editing is to create transgenic strains that express enzymes not typically present in their natural counterparts. We effectively equip them with the ability to generate novel products which are usually paired with some advantage that is inherent to the target organism. For example, yeast and bacteria are preferred due to their capacity for high-density cultivation in fermentation reactors. In contrast, microalgae, driven by photosynthesis, possess the ability to synthesize chemical precursors, bypassing the need for fossil fuels. Our mission at Phycoworks is to make this a reality by enabling the production of various commodities, including feedstock for the pharmaceutical industry, petrochemicals, and cosmetics in microalgae. Our central focus is on expediting the shift from our current fossil fuel-dependent economy to a more ecologically sustainable one by combining synthetic biology driven by AI and machine learning approaches..

What's your day-to-day like as a Strain Engineer?

Initially, my main task was the development of a bespoke, modular cloning pipeline that would expedite the creation of DNA constructs carrying transgenes destined for expression in microalgae. With the pipeline now validated and in place, my current daily duties revolve around the strategic conception of new constructs and the evaluation of their performance once they are delivered into microalgae.  Performance is assessed in various ways: Are the transgenes expressed to an optimal level? Does microalgae growth remain unaffected? Can we successfully detect the product we intended the strain to make, and if so, what is the yield and quality? Moreover, does the feasibility of scaling up production to reactor-level operations align with economic sensibility?

It is only when we have positive answers to the questions above do we aim to utilize our network of collaborators to transition from laboratory-scale to reactor-scale operations. However, this entire process is also underpinned by an in-house techno-economic assessment model. This model is crucial because it ensures that all these initiatives have the necessary economic justifications for deployment, and it is only at this point does a strain gains real commercial value.

Gene editing, algae, biotech, and so on.... But what's the most exciting part of your job?

The funny thing is, for me, the most exciting thing really is the challenge of it all. I personally believe that things are not worth doing unless they're kind of difficult to achieve--and you need to have the confidence that you're able to achieve it with the skills that you have. For example, our current projects all involve something that wasn’t done before--so it's a totally new ground. And because I work for a start-up company, we're all about working at a fast pace and meeting strict deadlines. Although there are naturally a lot of surprises in a start-up [laughs], using microalgae as a platform for generating the next generation of novel products will bolster the drive toward a greener economy. That's the crux of it all, and it's what matters most.

"One of the best rewards when working in a start-up is you have a greater sense of responsibility in the work that you do, which is more impactful and fulfilling in the long run."

Because I had the benefit of gaining my formative gene editing experience around the time when CRISPR-Cas9 really took off as the premier gene editing technology,

I feel it's very important to be on top of what is the state of the art in this field. It is not necessarily the most current or trendy method - but rather the most robust method that has been shown to reliably work across many contexts. Complexity can be built on top of it once you’ve got it working in your own hands and once you become familiar with deploying the technology in your own unique context, in my case in microalgae. For example, CRISPR technology has experienced its fair share of improvements, such as RNA editing or single-base editing variants, but its most fundamental form remains the most effective, at least in my opinion. This is especially true when you consider the limited time you have within a startup to get things working - you have to rely on the tried-and-tested more than the fancier approaches. It's also about having a solid foundation of knowledge - you need to know the biology behind how things work; why should I use this buffer, why should I perform this reaction at this temperature, and what are the critical steps in my protocol? These are the sorts of questions you should be asking yourself as you perform experiments. You need to always stay informed about the available technologies, how to effectively use them, and choose the right technology for the specific purpose of the project you're working on.

So, overall my advice to someone aspiring to be a genetic engineer would be: Focus on building a strong foundational knowledge and gain practical experience that is sufficient to guide you in applying the right technology to the right project.

What's next in the gene-editing arena?

Another exciting aspect to consider is the growing role of AI in the fields of science and gene editing. AI enables us to process vast amounts of high-quality data rapidly, leading to quicker solutions compared to traditional iterative testing methods. With regards to genetic engineering, having a system-wide overview of a metabolic network within the organism and using AI to help us predict how interfering with one enzyme can drive the flux towards the formation of a particular product would prove invaluable in accelerating current efforts in synthetic biology. Human and iterative approaches can only grant us superficial understanding of such complex biology, and I am excited to see developments on this front in the coming years.

Jason Shu Lim Yu is a Strain Engineer based in London, United Kingdom. This article is based on the series: Insights from a Strain Engineer by Gravel. Subscribe via our LinkedIn newsletter and email newsletter for the latest updates weekly.