Intrinsically disordered proteins in health and disease: mechanisms, molecular context and opportunities for drug discovery

The PhD fellowship is part of the EU-funded project, IDPro, which is an ambitious inter- and multidisciplinary Doctoral Network under the Horizon-Europe Marie Skłodowska-Curie Actions offering training for eleven PhD fellows.

IDPro is an exceptional network of nine beneficiaries (eight academic and one industrial) and five partner organisations (four industrial and three academic) from seven different countries, with excellent track records in protein research and supervision. Together, we will train eleven doctoral candidates, with distinct competencies of relevance for the IDP field to secure future scientific breakthroughs in a rapidly developing field. In particular, we will investigate how IDPs interact, how interaction is affected by disease-related mutations, and assess how IDPs cause aberrant cellular signaling in relevant human disease models. Furthermore, we will design ligands that can be further developed into molecular probes, which could represent lead structures for the development of drugs. IDPro will strengthen an emerging field in biology and medicine with implications for both academia and industry in the European union.

PhD Positions

Basic information:

The main goal of the project is to train highly-skilled doctoral candidates through international, inter-sectoral and multi/inter-disciplinary collaboration. Phd positions will be officially advertised from 1st of September 2023. Selected candidates are supposed to start before 31 August 2024.

All researchers recruited under this call must be doctoral candidates (i.e. not already in possession of a doctoral degree at the date of the recruitment).

Researchers are planned to be recruited for a maximum of 36 months covered by IDPro funding. They must be enrolled in a doctoral programme and should work full-time on the project. Local rules apply to the length of PhD studies.

Please note: This grant aims to promote mobility. PhD students must not have resided or carried out their main activity (work, studies, etc.) in the country of the recruiting beneficiary for more than 12 months in the 36 months immediately before their date of recruitment.

More information for candidates can be found here.


Per Jemth

Uppsala University, Sweden

1 position

The Jemth lab focuses on understanding the molecular underpinnings and evolution of protein interactions, with a special focus on coupled binding and folding of intrinsically disordered regions of proteins. In this context, the PhD candidate will investigate the role of flanking regions in motif-mediated protein interactions. The project involves a combination of bioinformatics and experimental approaches, and extensive collaboration within the IDPro network.

Jemth lab

Ylva Ivarsson

Uppsala University, Sweden

1 position

The Ivarsson lab focuses on short linear motifs (SLiM) based interactions. With our research we aim to contribute with novel insights into the human protein-protein interaction networks in health and diseases, and provide detailed information on the specificity determinants of the interactions. We also explore how pathogens such as viruses exploit motif based interactions to take over the host cell. Our research is interdisciplinary and combines biochemical and biophysical methods with bioinformatics and cell-based assays. Our core method is proteomic peptide phage display, which we have developed over the last ten years. The PhD student will investigate how kinases use SLiM-based interactions as a part of substrate recognition, and how these interactions are regulated and deregulated.

Ivarsson lab

Birthe Brandt Kragelund

University of Copenhagen, Denmark

1 position

Kragelund lab focuses on how structural disorder expands the molecular communication toolbox in biology and helps rethink protein interaction in the realm of structural disorder. One facet of the complexity of life is the cascade of signaling caused by thousands of proteins transferring unambiguous signals that instantly will regulate production and activities in the cell at the molecular level. Signal transfer initiated at the membrane is completed in the nucleus by the action of transcription factors and is conveyed through protein-protein interactions involving disordered regions. The PhD student will investigate the order-disorder cross-talk in the context of full-length transcription factors and how this cross-talk mediates regulation of transcription. By application of NMR spectroscopy and a suite of biophysical techniques we seek to map mechanisms of disorder-order crosstalk in transcription factors.

Birthe Brandt Kragelund lab

Kristian Strømgaard

University of Copenhagen, Denmark

1 position

The Strømgaard lab combine tools from chemistry and biology and apply these in peptide and protein engineering. Our aims are to develop modulators for protein-protein interactions and to provide molecular-level insight herein. We are interested in protein-protein interactions that are therapeutically relevant, in particular between integral membrane proteins and their intracellular protein partners, also known as receptor-complexes. We have a particular interest in receptor complexes in the brain and are eager to develop tool compounds into potential therapeutics; in one case we have brought a compound through Phase 1 clinical trials. The PhD student will examine scaffolding proteins of the brain, and study how disease mutations in these proteins affect protein-protein interactions, and subsequently develop tools to compensate for these disease-modifying mutations.

Strømgaard lab

Malene Ringkjøbing Jensen

Centre National de la Recherche Scientifique, France

1 position

The Jensen lab focuses on revealing the molecular mechanisms that underpin the function of large intrinsically disordered scaffold proteins in cell signaling. We study the structural and dynamic basis of how scaffold proteins recruit kinases and GTPases, how signaling information is transferred across scaffolding complexes and how the assembly of these complexes are regulated by post-translational modifications. The main experimental technique used in the lab is nuclear magnetic resonance (NMR) spectroscopy that is combined with X-ray crystallography and biophysical measurements of protein-protein interactions. The Ph.D. student will study two scaffold proteins within the JNK signaling pathway at atomic resolution and investigate how these scaffolds mutually cooperate to convey signaling specificity.

Malene Ringkjøbing Jensen lab

Stefano Gianni

Sapienza University of Rome, Italy

1 position

The Laboratory of Stefano Gianni investigates the relationships between the structure and function of proteins as well as the folding of proteins. We are currently particularly interested in the energetic communication that occurs between protein domains in multidomain proteins. We characterize these effects both from a folding and from a functional perspective. A key goal of our work is to define the basic rules that govern protein folding and allostery.
To address these questions we employ a synergy between protein engineering approaches and chemical kinetics. Our laboratory is equipped with a wide array of instruments that allows studying time-resolved reactions using optical spectroscopy. These reactions can be approached both by mixing and by relaxation methods and can be explored both in the fast and in the ultra-fast time regime. More details about the experimentalmethods may be found at this link.
In the research project the candidate will explore the mechanisms of recognition between IDP systems and folded domains, with particular emphasis on the role of multi-domain architectures in modulating such interactions.

Stefano Gianni lab

Zsuzsanna Dosztányi

Eötvös Loránd University, Hungary

1 position

The main interest of the Dosztányi lab is to study how the sequence of intrinsically disordered proteins is related to their structural and functional properties and their involvement in various diseases. They developed various computational tools to aid research in this field, including prediction tools (e.g. IUPred and ANCHOR) and databases (e.g. DIBS, PhaSePro). The main task of the Phd student will be to develop novel methods to study interaction sites within IDPs by considering context information and to understand how these interactions shape interaction networks at the proteome level, focusing on cases with biomedical relevance.

Dosztányi lab
Alfonso De Simone

University of Naples, Italy

1 position

Our research focuses on the underlying biomolecular mechanisms of human diseases involving IDPs. To this end, we integrate biomolecular NMR experiments, in solution and in the solid-state, with multiscale molecular simulations. Using this combined approach, we investigate IDP interactions with other proteins and with biological membranes. Our focus revolves around biomolecular processes at the origin of neurodegenerative disorders such as Alzheimer's and Parkinson's as well as non-neuropathic conditions such as dilated cardiomyopathies and tuberculosis. A critical research stream of the lab involves the characterisation of disordered regions of membrane proteins, a challenging task for which we develop tailored approaches under the ERC investigator framework. The project carried out in IDPro will focus on toxic oligomers and phase separations of α-synuclein, the central protein in Parkinson’s Disease. The research will investigate the self-assembly of pathological variants of this protein as well as its post-translational modifications to ultimately reveal how the balance between function and aggregation is modulated by external factors.

Alfonso De Simone lab

Michael Wehr

Systasy SYS Germany

2 positions

Systasy Bioscience GmbH, a Munich-based biotech company, uses advanced barcoding technologies and next-generation disease modeling to facilitate drug discovery in complex diseases. Systasy’s innovative and proprietary technologies provide a fast and cost-effective approach to mapping disease pathways from the cellular level to the patient cohort level to enable next-generation medicine. Systasy’s barcoding technology uses molecular barcodes to track different entities within one experiment. These entities include activities of targets and cellular pathways, cell types and patient material, as well as technical features such as biological replicates, wells, and plates. When applied to next-generation stem cell-derived disease models, Systasy’s barcoded and cell-based profiling assays enable multiplexed and scalable drug screening in early-stage drug discovery.

Systasy Bioscience

At Systasy Bioscience GmbH, we offer two positions to highly motivated, driven, and skilled PhD students to conduct their research in the area of cell-based assay development and their application in human disease models to study the function of intrinsically disordered proteins (IDPs). Systasy has state-of-the-art laboratories including next-generation sequencing technologies and human stem cell culture. Our laboratories are located in central Munich.At Systasy Bioscience GmbH, we offer two positions to highly motivated, driven, and skilled PhD students to conduct their research in the area of cell-based assay development and their application in human disease models to study the function of intrinsically disordered proteins (IDPs). Systasy has state-of-the-art laboratories including next-generation sequencing technologies and human stem cell culture. Our laboratories are located in central Munich.

In project 1, the PhD candidate will establish an array of cell-based assays for IDPs in human cell lines. Assays will use Systasy’s splitSENSOR and EXTassay barcoding technologies to enable a multiplexed readout to assess both the association to key interaction partners and the effect on physiological signaling pathways. splitSENSOR and EXTassay barcoding technologies are established at our site and were combined in a so-called targetProfiler approach before (see Galinski et al., 2018, Sci Reports as reference). Examples of IDPs to be selected are, but not limited to, amyloid precursor protein (APP), γ-secretase/presenilin, a-synuclein, Mint2, FKBP51, and calmodulin kinase II. Furthermore, the candidate will profile interactions for selectivity and specificity, and will assess IDP-directed antagonists in these assays.

In project 2, the PhD candidate will establish an array of validated CRISPR mediated genetic perturbation tools to assess a gain- and loss-of-function analysis of IDP interactions that are relevant to the regulation of neuronal signaling and cell fate. To do this, the PhD candidate will e.g., apply CRISPR inhibition (or knockout) directed on IDP candidates in a human disease model and combine this technique with a multi-pathway profiling assay (using company-owned barcoded pathwayProfiler assay, see Herholt et al., 2018, Sci Reports as reference) to identify affected targets and pathways (e.g., including cell fate, cell stress, immune signaling, metabolism, pluripotency, neuronal signaling). Data obtained from the pathway profiling will be complemented by (single cell) RNA-seq analyses.

Associated Partners:

Ben Schuler

University of Zurich, Switzerland

1 position

The Schuler lab investigates the structure, dynamics, and functions of biomolecules with single-molecule spectroscopy. In particular, we focus on systems with pronounced conformational heterogeneity that is difficult to resolve with other techniques. Examples are intrinsically disordered proteins (IDPs), protein-nucleic acid interactions, protein misfolding, or the behavior of proteins inside live cells. A key goal of our work is to reach mechanistic understanding based on quantitative physical models.
Addressing these questions requires a broad spectrum of complementary methods, and thus a multidisciplinary team of scientists from physics, chemistry, and biology who closely collaborate within the group. We use an integrative approach ranging from molecular biology and protein chemistry to a wide range of biophysical methods, single-molecule spectroscopies, and simulations. An important component of our research is the continuous development of single-molecule techniques and analysis methods for probing biological macromolecules over a wide range of conditions and timescales.

Schuler lab

Jesper Hedberg

Testa Center, Sweden

Testa Center is a private-public initiative between the Swedish government and Cytiva to establish an innovation hub for biological production and to secure the growth of the life science industry and its manufacturing capabilities. The main objective is to bridge the gap from discovery to industrialization. The Testa Center has the expertise and the equipment to help teams scale up from lab bench-scale to industrial-scale production. Testa Center is operated as a non-profit company.

Testa Center

Franziska Zosel

Novo Nordisk, Denmark

David Brown

Servier, France

Lovisa Holmberg Schiavone

AstraZeneca, Sweden