Background
Transcription factors (TFs) are central regulators of gene expression and play essential roles in development, cell identity and disease. Their activity is traditionally studied through interactions with DNA, cofactors and signalling pathways. However, an emerging and highly innovative area of research focuses on microproteins—small proteins that can regulate the activity, localisation or stability of larger regulatory proteins.
Because of their size and potentially selective modes of action, microproteins represent an exciting and relatively unexplored class of biological regulators. They may provide new opportunities for understanding transcriptional regulation and, in the longer term, for developing targeted therapeutic strategies.
This master’s project will be part of the NFR-funded TargetTF project, which investigates how microprotein-based approaches can be used to study and potentially modulate transcription factor function. The project will focus on the structural and functional characterisation of a previously unreported transcription factor–microprotein system involving SOX2 and a specific microprotein. The work will contribute to understanding the molecular basis of this system without assuming its interaction or functional effect in advance.
The project
The student will contribute to Work Package 1, which aims to investigate the molecular and cellular properties of a SOX2 transcription factor–microprotein complex. The project will combine methods from molecular biology, protein biochemistry, biophysics and cell biology.
Depending on the student’s interests and background, the project may include:
- Recombinant production and purification of the transcription factor and microprotein, including optimisation of protein constructs and expression conditions.
- Biochemical and biophysical characterisation of the protein complex, including investigation of complex formation, stability and molecular properties.
- Cell-based assays to examine the effects of the microprotein system on transcription factor-associated cellular responses.
- Preparation for structural studies, including construct design, protein-complex optimisation and assessment of conditions suitable for crystallisation or other structural approaches.
The project may also include targeted mutational analysis or additional experiments to identify regions important for the molecular properties and cellular activity of the system.
Significance
Microproteins are only beginning to be understood as regulators of important cellular processes. Studying their relationship with transcription factors could reveal new principles of gene regulation and provide insight into mechanisms that are difficult to investigate using conventional approaches.
The results from this project will contribute to the broader TargetTF programme, which aims to explore microprotein-based strategies for modulating transcription factor activity. In the longer term, this type of knowledge may support the development of more selective tools and therapeutic approaches for diseases in which transcriptional regulation is disrupted.
The project offers an opportunity to work at the interface of several rapidly developing fields and to contribute to a research area with strong potential for both fundamental discoveries and future biomedical applications.
Learning outcomes
Through the project, the student will gain experience in:
- Recombinant protein expression and purification
- Protein-complex analysis and biochemical characterisation
- Molecular cloning and construct design
- Cell-based functional assays
- Experimental planning, data analysis and troubleshooting
- Interdisciplinary approaches combining biochemistry, structural biology and cell biology
The specific experimental focus can be adapted to the student’s interests, with opportunities to emphasise either protein production and biochemical analysis, cellular assays, or structure-oriented work.
Research environment
The student will join an interdisciplinary research environment at the Institute of Molecular Biosciences (IMB), working in collaboration with researchers specialising in molecular biology, protein biochemistry, biophysics and structural biology. The project will also be connected to collaborators with expertise in structural studies and crystallisation.
This is an excellent opportunity for a motivated student to become involved in a cutting-edge research project at an early stage of discovery. The work combines challenging and modern experimental approaches and addresses fundamental questions in an emerging field with potential relevance to future therapeutic development.
Internal supervisor: Hans-Petter Hersleth
Main supervisor: Marie Rogne
Co-supervisor: Emily Martinsen
If you are interested in the project contact researcher Marie Rogne : marie.rogne@medisin.uio.no