About the Project
Use AI protein design, with AlphaFold3 and RoseTTAFold, to build binders that switch hidden microproteins on or off, at the Hubrecht Institute in Utrecht.
Why it matters
Microproteins are small proteins made from short stretches of the genome that standard protein catalogs long overlooked. What most of them do is unknown, and there are few tools to probe or control them. Many are small and partly disordered, so ready-made binders rarely exist. A binder that switches a microprotein on or off is both a research tool and a possible starting point for therapies.
The project
You will design synthetic proteins that bind and control microproteins. Starting from about 20 targets chosen by the network, you will design high-affinity binders, improve each design round with structural and biophysical data, and test whether your binders change what the microprotein does in cells.
What you will do
- Express, purify and characterize around 20 target microproteins (SEC-MALS and other biophysical methods)
- Design binders with AI protein design tools and refine them in design-test cycles with the thermal proteome profiling project in Ghent
- Measure binding with biolayer interferometry and test function in cellular assays, together with the Freiburg project
- Share structural models, binder sequences and data on the ORFeome platform
About ORFeus
This PhD is one of 15 in ORFeus, a Marie Skłodowska-Curie Actions Doctoral Network funded by Horizon Europe. ORFeus brings together 15 research groups in eight European countries, with industry and research partners, to study the dark proteome: the many microproteins made from small open reading frames long dismissed as non-coding. Together, the 15 projects aim to find these proteins, understand what they do, and test their potential in diagnosis, immunotherapy and drug development, with a strong focus on cancer.
Where you will work
You will join the group of Dr. Danny Sahtoe at the Hubrecht Institute in Utrecht. The group designs proteins computationally, including peptide binders and reconfigurable protein assemblies. You will work closely with the group of Prof. Owen Rackham at the University of Southampton, which brings machine learning expertise for the dark proteome.
Who should apply
We welcome applications from protein biochemists, structural biologists and biophysicists who want to learn AI protein design, and from computational protein designers who want to work in the lab.
- A master's degree (or equivalent) in biochemistry, structural biology, biophysics, molecular biology, computational biology, bioengineering, or a related field
- Hands-on experience with recombinant protein expression, purification and biophysical characterization, and/or with computational protein structure prediction and design
- Good written and spoken English
- Nice to have: AlphaFold or RoseTTAFold, SEC-MALS or biolayer interferometry, cell-based assays
Eligibility (MSCA rules)
Living or studying in the UK? You are likely eligible for this position.
You must not have lived or carried out your main activity (work, studies) in the Netherlands for more than 12 months in the 36 months before your start date. Compulsory national service, short stays such as holidays, and time spent in a refugee status procedure do not count. You must not hold a doctoral degree. Any nationality may apply.
What we offer
- A 36-month, full-time employment contract with full social security, under MSCA rules
- Supervision by Dr. Danny Sahtoe and Prof. Owen Rackham, with mentoring from partners across academia and industry
- A secondment of around three months with an ORFeus industry partner
- Training with 14 other ORFeus PhD candidates across Europe: network schools, workshops, transferable skills and international conferences
- PhD enrollment at Utrecht University
Practical details
Start around March 2027; the exact date depends on the host institution. Reference letters are requested only at the interview stage.
How to apply
You can only apply via https://www.orfeus-dn.eu/apply/ - registering your interest on this website is not equivalent to an application. You can apply to up to three of the 15 ORFeus projects and rank them; every project you rank considers you. The application asks for:
- a few eligibility questions
- a short motivation per project (150 to 200 words)
- your experience with the project's key techniques
- your CV
- an overview of your bachelor's and master's grades, in one PDF
- contact details for two referees
- a short motivational video
Funding Notes
Fully funded 36-month employment contract in ORFeus, an MSCA Doctoral Network (Horizon Europe, GA 101309891), with full social security. A salary, not a stipend. Salary details for this position are on the application page. Open to all nationalities, including applicants living or studying in the UK. Mobility rule: you must not have lived, worked or studied in the Netherlands for more than 12 months in the 36 months before your start date. Applicants must not hold a doctoral degree.
