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"PhD Position in Biocatalysis - Evolving Enzymes for New Chemistry"

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PhD Position in Biocatalysis - Evolving Enzymes for New Chemistry

Understanding the nature of enzyme promiscuity whilst enabling a more sustainable future. The research group headed by PI Dr. Reuben Leveson-Gower is hiring a PhD student to work on a project in the field of Biocatalysis. Motivated by the immense potential that enzymes represent to greatly improve the sustainability of the chemical and pharmaceutical industries, our group seeks to engineer enzymes that can facilitate new reactions that were previously not known in nature. To this end we will adapt existing enzyme architectures (i.e. naturally occurring cofactors and catalytic machinery) to conduct new catalytic tasks through a combination of chemical intuition and enzyme engineering.

The PhD project will involve bioinformatic selection of candidate enzymes, employing a combination of ‘off-the-shelf’ tools based on both sequence and structure. These enzymes will be produced, screened and the best variants subject to protein engineering campaigns. Once highly active variants are produced, the molecular mechanisms by which they have achieved their improvements will be investigated. These insights will form a key part of the ‘build, test, learn’ cycle to accelerate the development of further biocatalysts for related ‘new-to-nature’ reactions. The results will reveal the determining characteristics of enzyme catalytic promiscuity, so that it can harnessed with increasing efficiency. Ultimately, the research aims to develop practically applicable catalysts for the efficient and benign synthesis of societally important molecules.

The work will be conducted in the shared laboratories of the BOC section, a highly collaborative and collegial environment. This role involves designing and instigating robust experimental protocols that will serve as a basis for the group’s future research activities. This will be done in close supervision from the PI, and there is also the opportunity to help train master and bachelor project students. Involvement in teaching is a requirement of the position.

Job requirements: Ideally suited candidates must have a Master’s degree in Chemistry, Biochemistry, or Biotechnology. Strong grasp of and interest in fundamental concepts in organic chemistry. Experience in the following topics is beneficial: Synthetic chemistry; Site-directed mutagenesis and cloning; protein expression/purification; Enzyme engineering/evolution; analytical method development; Protein bioinformatics; computational (bio)chemistry. At this career stage it is unlikely that any candidate has all these skills and thus it is essential that candidates are enthusiastic in expanding their capabilities during the PhD. Therefore, preference will be given to those with demonstrated ability and passion for learning new wet-lab or dry-lab skills.

Doctoral candidates will be offered a 4-year period of employment in principle, but in the form of 2 employment contracts. An initial 1.5 year contract with an official go/no go progress assessment within 15 months. Followed by an additional contract for the remaining 2.5 years assuming everything goes well and performance requirements are met. Salary and benefits are in accordance with the Collective Labour Agreement for Dutch Universities, increasing from Promovendus gross per month, from the first year to the fourth year based on a fulltime contract (38 hours), plus 8% holiday allowance and an end-of-year bonus of 8.3%.

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