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directed EVOlution in DROPS

Periodic Reporting for period 1 - EVOdrops (directed EVOlution in DROPS)

Reporting period: 2018-10-01 to 2020-09-30

Darwinian evolution is a powerful process that has given rise to the functionally diverse set of proteins which are the functional molecules of the living, present in all living systems. In Nature, over billions of year of evolution, repetitive rounds of mutation, selection and amplification have optimized enzymes. Enzymes are Nature’s catalyst and they allow cells to perform an enormous range of different reactions. Some of the natural enzymes already have a validated industrial interest, for example food transformation and catalysis of challenging chemical reactions. Nonetheless, relying on natural evolution to improve enzymes for industrial and medical use suffers from two major drawbacks: it does not provide sufficient control over the selection pressures, and it cannot, by definition, be used to improve systems and reactions that are not found in Nature.

Mimicking the evolutionary principles of Nature in the laboratory is a process called directed evolution. It provides an attractive way to circumvent the limitations of the use of Natural evolution to select improved catalysts. While natural evolution took billions of years to optimize macromolecules (and billions of cycles of mutation and selection), it has become clear that directed evolution in the laboratory can be successful – to be efficient in an industrial process – by the combination of rapid generation of genetic diversity and ultra-high throughput screening and selection capabilities to identify variants of interest. Because it is more likely to find a 2m tall person in a crowd of millions of people compared to a small group of 10 people, similarly, it is more likely to find an improved catalyst in a large library of molecules than in a small subset. Screening millions of molecules in short amount of time increases the chance to find interesting molecules that do the job efficiently. This is precisely what microfluidics can do : provide a new technology to analyse large libraries of potential molecules and fish out those of interest.

Microfluidics is a versatile technology that now enters industrial processes as part of the overall diagnostics or screening methodology. Droplets (of typical diameter between 1 and 200 µm) used as micro-reactors that are manipulated in micro-channels are vehicles of standard biochemical assays in a miniaturized (volume per droplet: volumes 0.5 fL and 4 nL) and automatized format with ultra-high-throughput (1-10 kHz; corresponding to more than 10 millions per day). Moreover, the picoliter volume scale of microdroplets results in a million-fold reduction on reagents’ costs, therefore opening new screening capabilities. Hence, microfluidics makes it possible to perform experiments currently impossible with other techniques. The explosive growth of start-up companies from the technology developing laboratories, combined with the entry of industrial giants (some of which are members of EVOdrops) into the microfluidic area led to an impressive growth of the microfluidic market over the past years with even more potential for the future for applications in diagnostics, healthcare and the transformation of bio-resources.
EVOdrops is a translational approach for microfluidics and biochemical methods towards the engineering of proteins and systems of industrial or therapeutic interest. We train a new generation of Early Stage Researchers (ESRs) in a multidisciplinary network of researchers from different communities - biology, biotechnology, microfluidics and microtechnology engineering - to explore directed evolution processes for protein engineering in an integrative way that transcends the training provided in one single team or even institution. The ESRs are trained to develop and apply a global and multi-disciplinary approach based on key enabling technologies for high-throughput analysis in biological fields. Our overarching goal is to optimize processes at all levels of the chain of operation to reach ultra-high throughput, improved sensitivity, and reliability of systems for the selection of variants of fundamental, medicinal, practical and industrial interest. The work carried out in Period 1 of the project addresses our general aims and objectives. We have established a Supervisory Board and the conditions for a smooth collaboration. We have hired a team of ESRs who are trained locally by their supervisor with the objectives to develop, share and spread their research results first within the network and to disseminate those. To help them develop their potential we have setup a multidisciplinary ESR supervision panel for each ESR and we monitor their scientific progress as well as their career plans and train them through workshops. To date six secondments have taken place. Given the pandemic conditions, several actions have been implemented as mitigations to the risks of loss of interactions between staff with remote meetings and reunions. We obtained out first scientific results from the interactions between the partners on library manipulations and microfluidic integration. These results need now to be consolidated during the second phase of the project, especially through secondments.
One of the major goals for impact in this consortium is to provide ESRs with the tools and skills to develop successful long-term career plans and train them for potential jobs in both, industry and academia. To this end the consortium EVOdrops has taken advantage of the industrial partners and beneficiaries to expand the ESRs’ perspectives on their potential careers and provide dedicated training. This has included talks by beneficiaries in workshops (WS1) (companies: BioMillenia and Thermo Fisher Scientific Baltics), on their strategy and working environment, and at workshop WS2, IBIDI presented the company’s environment, as well as the demands and challenges for employees in an SME.

Due to the challenging pandemic situation, many of these interactions were curtailed by the restrictions arising from COVID-19, especially as workshops were postponed. However, to mitigate this transferable skills training has been included in all workshops that have taken place. We engaged ESRs in training on communication, public engagement and presenting with impact from award-winning educators, academic writing (delivered remotely), and expanding their career prospects to entrepreneurship with dedicated sessions raising their awareness of potential career paths. Following highly positive feedback from ESRs on the activities that have taken place, we will co-construct, together with them, the beneficiaries and our partners, a series of remote ‘career talks’ to take place in Q1-2 2021. They will take the form of virtual visits, panel discussions, and/or presentations in the style of ‘a day in the life of…’. We will invite employees at different levels, chosen in consultation with the ESRs to cater for their interests, to present remotely and participate in Q&As.

We have setup various tools of dissemination including our website, a twitter account and an industrial newsletter. In the first period this was mostly handled by the PIs, the network and scientific liaison manager. In the upcoming second period the plan is to involve ESRs more in the design and organisation of these platforms.
EVOdrops Consortium at WS2
EVOdrops Consortium at KOM