PhD position in AI-Driven Design of Selective Inhibitors for Matrix Metalloproteinases (MMPs) - DTU Bioengineering

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PhD position in AI-Driven Design of Selective Inhibitors for Matrix Metalloproteinases (MMPs) - DTU Bioengineering
  • Danmarks Tekniske Universitet
  • Anker Engelunds Vej 101, 2800 Lyngby-Taarbæk

Are you driven by the potential of AI in medicine? Are you excited by the translational impact of bioengineering research and its potential to bridge fundamental science with real-world medical applications? Do you want to design next-generation protein therapeutics using cutting-edge generative models and validate them in the lab? Join a collaborative PhD project at DTU Bioengineering focused on developing highly selective inhibitors against matrix metalloproteinases (MMPs).

About the position
This PhD project will focus on designing and validating de novo  protein inhibitors against human MMPs. Matrix metalloproteinases (MMPs) are key regulators of extracellular matrix remodeling, and their dysregulation is implicated in numerous diseases, including cancer, chronic inflammation, and fibrosis. Aberrant MMP activity can drive tissue destruction, pathological remodeling, and disrupted cell signaling, making them critical yet complex targets for therapeutic intervention. Despite significant efforts, therapeutics targeting MMPs have largely failed in clinical settings due to issues like poor selectivity across the MMP family and dose-limiting side effects.

Recent advances in AI-driven protein design offer new opportunities to revisit the long-standing challenge of selectively targeting MMPs. The project will use state-of-the-art AI-based protein design tools to generate and prioritize inhibitor candidates with high predicted affinity and selectivity. These designs will then be experimentally validated through a combination of affinity binding assays, enzymatic activity measurements, biophysical characterization, mass spectrometry (MS)-based proteomics, and functional studies. Under the joint supervision of Assoc. Prof. Timothy P. Jenkins and Asst. Prof.  Konstantinos Kalogeropoulos, you will join a vibrant, multidisciplinary team to push the boundaries of therapeutic protein engineering.

Responsibilities and qualifications
Design and implement inhibitor libraries using generative AI tools such as RFdiffusion2 or BoltzDesign.

  • Perform molecular dynamics simulations and in silico screening to assess inhibitor-target interactions and predict selectivity.
  • Clone, express, and purify top candidates using high-throughput bacterial systems and cell-free protein synthesis.
  • Perform structural and biophysical characterization of designed proteins (e.g., CD, SPR, BLI).
  • Perform validation of candidate inhibitors using fluorescence-based inhibition assays and MS-based degradomics.
  • Validate promising candidates in cell-based assays to assess biological activity and selectivity in a cellular context.
  • Contribute to in vivo-like model validation (e.g., organoids or ex vivo systems) to explore translational potential.
  • Publish results in high-impact journals and present findings at scientific conferences.
  • Engage in interdisciplinary training to build expertise in both computational and experimental techniques.
  • Play an active role in education and outreach in protein design and proteomics, including contributions to teaching and mentoring activities.

You must have a two-year master's degree (120 ECTS points) or a similar degree with an academic level equivalent to a two-year master's degree in a relevant field, such as bioinformatics, biochemistry, molecular biology, biotechnology, or a related discipline.

You must have:

  • Expertise in either computational protein design or wet lab techniques for protein engineering, with a strong willingness to learn the complementary skill set.
  • Experience in collaborative research environments.
  • Excellent communication and teamwork skills.
  • A proactive attitude towards learning and applying new skills.
  • Experience with programming in Python and a working knowledge of statistics

It would further be beneficial if you have some of the following skills:

  • Hands-on experience with protein expression in E. coli and protein purification.
  • Experience with enzyme kinetics or developing inhibition assays.
  • Familiarity with biophysical techniques (e.g., SPR, BLI, CD).
  • Exposure to computational tools like RFdiffusion, ProteinMPNN, or AlphaFold.
  • Experience with mass spectrometry-based proteomics or degradomics.
  • Strong analytical skills and the ability to work effectively in a collaborative, interdisciplinary research environment.

Approval and Enrolment  
The scholarship for the PhD degree is subject to academic approval, and the candidate will be enrolled in one of the general degree programmes at DTU. For information about our enrolment requirements and the general planning of the PhD study programme, please see DTU's rules for the PhD education

We offer
DTU is a leading technical university globally recognized for the excellence of its research, education, innovation and scientific advice. We offer a rewarding and challenging job in an international environment. We strive for academic excellence in an environment characterized by collegial respect and academic freedom tempered by responsibility.

Salary and appointment terms
The appointment will be based on the collective agreement with the Danish Confederation of Professional Associations. The allowance will be agreed upon with the relevant union. The period of employment is 3 years, with a starting date of December 1st,  2025, or as soon as possible. 

You can read more about career paths at DTU here .

Further information
Further information may be obtained from Assoc. Prof. Timothy P. Jenkins (tpaje@dtu.dk ) or Asst. Prof. Konstantinos Kalogeropoulos (konka@dtu.dk ).

You can read more about “the Department” at www.bioengineering.dtu.dk.

If you are applying from abroad, you may find useful information on working in Denmark and at DTU at DTU – Moving to Denmark . Furthermore, you have the option of joining our monthly free seminar “PhD relocation to Denmark and startup “Zoom” seminar ” for all questions regarding the practical matters of moving to Denmark and working as a PhD at DTU. 

Application procedure 
Your complete online application must be submitted no later than 22 September 2025 (23:59 Danish time)

Applications must be submitted as one PDF file containing all materials to be given consideration. To apply, please open the link "Apply now", fill out the online application form, and attach all your materials in English in one PDF file . The file must include:

  • A letter motivating the application (cover letter)
  • Curriculum vitae 
  • Grade transcripts and BSc/MSc diploma (in English) including official description of grading scale

You may apply prior to ob­tai­ning your master's degree but cannot begin before having received it. 

Applications received after the deadline will not be considered.

All interested candidates irrespective of age, gender, disability, race, religion or ethnic background are encouraged to apply. As DTU works with research in critical technology, which is subject to special rules for security and export control, open-source background checks may be conducted on qualified candidates for the position.

The Department of Biotechnology and Biomedicine (DTU Bioengineering) is an international leader in the areas of biotechnology and biomedicine. Our engineering approach to all aspects of biotechnology and biomedicine positions us as a valuable player with unique competences in a growing bio-based economy and with health systems transforming towards personalized medicine. We have a clear focus on the needs in life science- and biotech industries and point towards innovation, new businesses, and scientific services for the benefit of society. The department has extensive collaborations with national and international research units and industry. DTU Bioengineering has approx. 400 employees, of which 2/3 are scientific staff. The department is located at DTU Lyngby Campus.

Technology for people
DTU develops technology for people. With our international elite research and study programmes, we are helping to create a better world and to solve the global challenges formulated in the UN’s 17 Sustainable Development Goals. Hans Christian Ørsted founded DTU in 1829 with a clear mission to develop and create value using science and engineering to benefit society. That mission lives on today. DTU has 13,500 students and 6,000 employees. We work in an international atmosphere and have an inclusive, evolving, and informal working environment. DTU has campuses in all parts of Denmark and in Greenland, and we collaborate with the best universities around the world.

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