ERC grants

ERC Synergy Grant 2023 - Functional cartography of intestinal host-microbiome interactions

CartoHostBug

Eduardo Villablanca, PhD - Karolinska Institute, Sweden
Stefania Giacomello, PhD - KTH Royal Institute of Technology, Sweden
Julio Saez-Rodriguez, PhD - University Hospital Heidelberg, Germany
Georg Zeller, PhD - Leiden University Center of Infectious Diseases, LUMC

• EC contribution for total project: €10.000.000
• EC contribution to LUMC: TBC
• Start date: TBC – End date: TBC

Abstract:
Will follow soon

ERC Synergy Grant 2022 – Glycans as Master Switches of B Cell Activity in Autoimmunity GlycanSwitch

Prof. Tom Huizinga, PhD – Department of Rheumatology, LUMC (corresponding PI)
Prof. Manfred Wuhrer, PhD – Center for Proteomics and Metabolomics, LUMC
Prof. Salome Pinho, PhD – University of Porto, Portugal
Prof. Gordon Lauc, PhD – GENOS, Croatia

• EC contribution for total project: €​9.975.000
• EC contribution to LUMC: €​5.000.000
• Start date: 01-01-2023 – End date: 31-12-2028

Abstract: Autoimmune diseases including rheumatoid arthritis (RA) are often life-threatening disorders with increasing disability having a negative impact on patients’ quality of life. Mechanisms leading to the breach of tolerance in development of autoimmunity are still largely unknown. Protein glycosylation is an essential regulatory mechanism in the immune system. We recently demonstrated that N-glycosylation of the variable region (Fab) of autoantibodies is a hallmark of RA development and progression. We also demonstrated that autoantibodies acquire these Fab glycosylation signatures already many years before disease onset. We herein hypothesize that Fab glycosylation at the level of the B cell receptor is a key molecular switch promoting the selection, activation and proliferation of autoreactive B cells leading to the concomitant breach of immunotolerance. Within GlycanSwitch, we will map the Fab glycome of various types of RA autoantibodies and autoreactive B cells. We will study the factors and underlying cellular mechanisms that regulate Fab glycosylation of B cell receptors and autoantibodies. We will investigate the immunological effects of Fab glycosylation and the impact in B cells signalling and activation in the context of molecular and cellular interacting partners in the immune microenvironment. Finally, we will test in relevant mouse models how Fab glycosylation of autoantibodies and autoreactive B cells contributes to the breach of tolerance. We expect that the obtained insights into the role of glycans as key checkpoint for the selection of autoreactive B cells and the rise of autoimmunity will provide leads for targeted therapeutic interventions as well as rationales for the early detection of RA and autoimmune diseases in general. We foresee that the knowledge generated will allow us to embark on a targeted prevention clinical study in patients at risk for RA to turn off the GlycanSwitch leading to chronic RA.

ERC Advanced Grant 2021 – Maria Yazdanbakhsh - Reversing vaccine hypo-responsiveness

REVERSE

Prof. Maria Yazdanbakhsh, PhD

Department of Parasitology

• ERC Advanced Grant 2021 – panel LS6
• EC contribution: EUR 2,372,681
• Start date: 01 October 2022 – End date: 30 September 2027

Abstract

There is growing evidence that vaccine immunogenicity and efficacy present considerable variations across populations in high- and low/middle-income countries. For example, volunteers’ vaccination in Europe with attenuated malaria vaccine can result in 100 % protection, while the efficacy drops to just 29 % in Africa. Similar trends are seen with other vaccines. The EU-funded REVERSE project will understand the mechanisms underlying vaccine hypo-responsiveness across populations and find ways to reverse it. The project relies on the hypothesis that the variation in the immunological network due to exposure to microorganisms and parasites, and the cellular metabolism of populations residing in distinct environmental conditions, is responsible for vaccine hypo-responsiveness. Immunological and metabolic interventions can reverse it.

ERC Advanced Grant 2020 - Andrew Webb - Portable, accessible and sustainable magnetic resonance Andrew Webb

PASMAR

Prof. Andrew Webb, PhD

Department of Radiology

• ERC Advanced Grant 2020 – panel LS7
• EC contribution: EUR 2,493,715
• Start date: 01 September 2021 – End date: 31 August 2026

Abstract

Magnetic resonance imaging (MRI) provides high-definition diagnostic imaging. However, it’s very expensive and requires skilled maintenance and highly trained technicians. The EU-funded PASMAR project aims to provide MRI systems that will enable medical screening as part of an affordable, sustainable and accessible platform for the developing world. The objective is to design new types of low-cost low-field systems for specific clinical applications and overcome the main challenge of much lower MRI signals. These specialised systems can be used for adult/paediatric brain, orthopaedics and lung/spine scanning, taking advantage of the flexibility of permanent magnet arrays with new geometries, targeted for specific organs, and using open-source design to allow local maintenance and repair.

Andrew Webb already received an ERC Advanced Grant in 2014.

ERC Advanced Grant 2019 – Rene Toes - Targeting auto-reactive B-cells by vaccination to cure human auto-immune disease

Target to B-Cure

Prof. Rene Toes, PhD 

Department of Rheumatology

• ERC Advanced Grant 2019 - panel LS7
• EC contribution: EUR 2,500,000
• Start date: 01-01-2021 - End date: 31-12-2025

Abstract

Most incurable human autoimmune diseases are chronic conditions characterized by the presence of autoantibodies. Elimination of the autoreactive B-cells are not presently feasible due to a lack of specific markers. The EU-funded Target to B-cure project aims to develop a vaccine that will allow specific long-lasting depletion of autoreactive B-cells. Using autoimmune rheumatoid arthritis (RA) as a model, it will study the RA specific autoimmune response. Researchers will identify autoreactive B-cells and the B cell receptor (BCR) repertoire at several stages of the disease to determine the potency of the non-germline-encoded mutations in BCRs as antigens amenable to T-cell recognition and vaccination. Finally, the project will design patient-tailored vaccines and perform a phase I trial to determine the feasibility of depleting disease-causing B-cells.

ERC Advanced Grant 2018 – Johanna Meijer - The circadian clock in day-active species: preserving our health in modern society

DiurnalHealth

Prof. Johanna Meijer, PhD

Department of Cell and Chemical Biology

• EC contribution: EUR 2,233,251
• Start date: 01 September 2019 - End date: 31 August 2024

Abstract

Due to a significant increase in the use of artificial light in our 24h economy, the biological clocks of all living organisms, including humans, are severely disrupted. Many severe health disorders are consequences of clock disruption such as diabetes, sleep/mood disorders, cardiovascular disease, and immune dysfunction. The central timekeeper in mammals is the suprachiasmatic nucleus (SCN), and the mechanisms by which light disrupts integrity of the SCN has been well investigated in nocturnal species. In contrast, mechanisms of clock disruption in humans and other diurnal (day-active) species remain poorly defined. I have evidence that the mechanisms that drive SCN function are fundamentally different between nocturnal species and diurnal species. This defines my aim to restore proper clock function in diurnal species, including humans. To test this, in Objective 1 we will identify similarities and differences between nocturnal and diurnal clocks with respect to their i) response to light, ii) neuronal synchronization, iii) output, and iv) response to physical activity. Based on these findings, in Objective 2 we will develop novel strategies to manipulate and restore clock function in diurnal species. These objectives will be achieved using novel, state-of-the-art chronobiology methods including in vivo electrophysiology and Ca2+ and bioluminescence reporters—all in freely behaving day-active animals, as well as in slice preparations containing the SCN. For studies on the human SCN we record with 7-Tesla fMRI. This proposal will help establish a new basis for chronobiology with respect to the most suitable models for studying translational applications. The results will yield immediate benefits in terms of manipulating biological clock function among vulnerable populations in modern society, particularly the elderly, patients in intensive care, and shift workers.

ERC Consolidator Grant 2022 – Gerbrand van der Heden van Noort - ADPribosylation and Ubiquitination; post-translational interplay

ADProbe

Gerbrand van der Heden – van Noort, PhD, Assistent Professor
Department of Cell and Chemical Biology

• ERC Consolidator Grant 2022 – panel LS1
• EC contribution: EUR 1.999.625
• Start date: 01-01-2024 | End date: 31-12-2028

Abstract:

ERC Consolidator Grant 2021 – Martijn Luijsterburg - Mechanisms at the interface of DNA damage repair and transcription

STOP-FIX-GO

Martijn Luijsterburg, PhD, Associate Professor

Department of Human Genetics

• ERC Consolidator Grant 2021 – panel LS1
• EC contribution: 1,999,764 euro
• Start date: 01 June 2022; End date: 31 May 2027

Abstract: 

Transcription-blocking DNA lesions can be triggered by a wide variety of DNA-damaging agents and form an obstacle to gene transcription enzymes. Transcription-coupled repair (TCR) is a specialised DNA repair pathway that selectively removes DNA lesions from actively transcribed genes, restoring transcription. The mechanisms underlying these processes are poorly understood. The EU-funded STOP-FIX-GO project will elucidate the mechanisms underlying the cellular responses to transcription-blocking damage through a combination of high-tech genomics, proteomics and mapping techniques with a focus on known and promising TCR proteins. Understanding how cells naturally overcome transcription roadblocks could point to novel therapeutics.

ERC Consolidator Grant 2021 – Daniel Pijnappels - Translational optoelectronic control of cardiac rhythm in atrial fibrillation

TransRhythm

Prof. Daniel Pijnappels, PhD

Department of Cardiology

• ERC Consolidator Grant 2021 – panel LS7
• EC contribution: 1,999,999 euro
• Start date: 01 March 2023; End date: 29 February 2028

Abstract: 

The EU-funded TransRhythm project aims to determine the translational potential of optoelectronic heart rhythm control for managing atrial fibrillation (AF) as the most prevalent cardiac arrhythmia. Immortalised human atrial cardiomyocytes expressing light-gated ion channels will be used to engineer human atrium-sized 3D models of AF. Multi-electrode-LED arrays will be integrated to control model optoelectronic rhythm via bioelectricity generation by precise illumination. Insights from the study will enable the application of this approach in AF animal models to determine the feasibility, safety, and therapeutic implications. The project objective is to establish principles of optoelectronic control of cardiac rhythm and discover novel insights into AF mechanisms and treatment.

Daniel Pijnappels already received an ERC Starting Grant in 2016.

ERC Consolidator Grant 2020 – Milena Bellin - Human mini hearts: looking for culprits and victims in cardiac disease

Mini-HEART

Milena Bellin, PhD, Associate Professor

Department of Anatomy & Embryology

• ERC Consolidator Grant 2020 – panel LS4
• EC contribution: 2,000,000 euro
• Start date: 01 September 2021; End date: 31 August 2026
• We are hosting this research together with the University of Padua

Abstract

Cardiac disease causes morbidity and mortality as frequently as cancer. Predicting cardiac arrhythmia and cardiac failure, understanding multicellular (patho)physiological mechanisms, and devising new treatments represent unmet needs in the field. Human induced pluripotent stem cells (hiPSC) could revolutionise the way we study human disease but unfortunately, they still fall short in recapitulating variable phenotypes and complex cardiovascular diseases. This is partly due to functional immaturity of hiPSC-derived cardiac tissues, shortage of methods for accurate functional analysis and inability to identify cell-type specific contributions to disease pathology. I will address these challenges in Mini-HEART. We recently assembled novel three-dimensional multi-cellular cardiac microtissues as an important step towards full maturation and used these to demonstrate that cardiac disease mutations might directly affect non-myocyte cardiac cells. However, application of hiPSC microtissues to precision medicine remains to emerge. Using a multidisciplinary approach, I will combine isogenic hiPSC, their differentiation into distinct cell types of the heart, multifaceted biophysical assays, and tissue engineering to prove cell-type causality of disease and identify new molecules targeting the culprit cells to rescue the disease phenotype. I plan to use our unique complex hiPSC-cardiac microtissue to

1. identify and synthetically enhance maturation mechanisms;
2. reveal late arrhythmic and fibrotic phenotypes;
3. dissect cell-type specific contributions to complex cardiac diseases, including the role of macrophages and sympathetic nerves;
4. test two therapeutic strategies based on drug-tailoring and gene editing, to modulate the disease phenotype.

Together, Mini-HEART will create new opportunities for designing novel biomedical tools to
i) capture phenotypic changes,
ii) reveal (patho)physiological mechanisms and ii) develop new therapeutic approaches for heart disease.

ERC Consolidator Grant 2017 – Jenny van der Steen - Attempts to control the end of life in people with dementia: two-level approach to examine controversies

CONT-END

Jenny van der Steen, PhD, Associate Professor

Department of Public Health and Primary Care

• ERC Consolidator Grant 2017 - panel SH3
• EC contribution: EUR 1,988,972
• Start date: 01 December 2018 - End date: 30 November 2023

Abstract

In dementia at the end of life, cognitive and physical decline imply that control is typically lost. CONT-END will examine control in the context of three emerging interventions which contain a controversial element of striving for control in the process of dying with dementia: advance care planning of the end of life, use of new technology to monitor symptoms when unable to self-report, and euthanasia. To perform outstanding research, the proposed research examines control at the level of clinical practice, but also at the level of end-of-life research practice. The latter provides ample opportunities for researchers to control the research process. That is, research designs are often flexible and we will study how flexibility impacts research in an emotionally charged area.

I will take an empirical mixed-methods approach to study the two practices in parallel. The work is organised in three related Work Packages around three research questions.

1. In a 6-country study, I will examine if and when people with dementia, family caregivers and physicians (900 respondents) find the interventions, shown on video, acceptable.
2. A cluster-randomised 3-armed controlled trial in 279 patients and their family caregivers assesses effects of two types of advance care planning differing in level of control (detailed advance treatment orders versus goal setting and coping based) on outcomes ranging from favourable to less favourable, and whether effects differ in subgroups. cases in which the technology is preferred or applied are observed.
3. Ethnographic fieldwork in two different end-of-life research practices and a Delphi study to synthesize CONT-END’s findings assess how researchers shape findings. This greatly improves the quality of CONT-END and provides the input to develop new methodology for improving research quality and integrity.

ERC Starting Grant 2022 – Simon Jochems – Understanding respiratory tract infections through minimally-invasive, daily nasal sampling in children

DailySAM

Simon Jochems, PhD, Assistant Professor
Department of Parasitology

• ERC Starting Grant 2022 – panel LS7
• EC contribution: EUR 1.677.858
• Start date: 01 July 2023 – End date: 30 June 2028

Abstract

Pneumonia is the number one infectious cause of death in children worldwide. Many of the viruses and bacteria that cause pneumonia regularly infect, or colonize, the upper respiratory tract (URT) without causing disease. This drives community transmission but is also an important source of immunity. The processes and key host immune and microbiota factors that determine the infection kinetics, transmission and development of immunity during such infections need elucidation.

I have recently optimized minimally-invasive nasal sampling analysis methods using Synthetic Absorptive Matrix (SAM) strips that now allow me to address these knowledge gaps. Through the daily collection of such well-tolerated nasal samples in children, I will study non-pathological, naturally-acquired URT infections, but also controlled infections in an ethical and safe manner using the live attenuated influenza vaccine. In addition, I will perform high frequency nasal sampling in groups of schoolchildren to precisely measure transmission events over time and even infer exposure. Incoming bacteria, viruses and the resident URT microbiome as well as mucosal host innate and adaptive immune responses will be quantified in parallel throughout infections using existing and new high-throughput assays, including an antigen array and microfluidic qPCR for 32 pathogens. Multi-omics integrative time-series analyses and mathematical modelling will be used to identify parameters that are central and predictive for pathogen acquisition, replication and clearance; as well as for transmission and immune boosting. Key novel markers and concepts will be validated using state-of-the-art in vitro mucosal models.

The comprehensive and detailed understanding of URT infections obtained in this project can lead to better diagnostics, mucosal targeted therapies and vaccines, and provide a basis for the improved predictions of pathogen spread and public health effects of interventions at the population level.

ERC Starting Grant 2022 - Meta Roestenberg - Dissecting early Skin-based immune responses to PARasites in ControLled human infection studies to design novel vaccines

SPARCL

Meta Roestenberg, PhD, Professor
Department of Parasitology

• ERC Starting Grant 2022 – panel LS6
• EC contribution: EUR 1.499.894
• Start date: 01 May 2023 – End date: 30 April 2028

Abstract

Parasitic diseases cause considerable morbidity and mortality in poverty-stricken areas, affecting hundreds of millions of lives globally. Vaccines are urgently needed to alleviate disease and lift the economic consequences. Plasmodium falciparum malaria, Schistosoma mansoni and Necator americanus hookworms are together responsible for the greatest burden of disease. Vaccination with attenuated parasites is an efficacious strategy in inducing immunity to parasites in animal models. Recently, we have translated attenuated parasite vaccination to humans in proof-of-concept clinical trials in which we protected subsets of individuals from challenge. This unique preliminary data indicates a role for the skin as a prime immunological organ. Based on these findings, I propose to create a next generation highly immunogenic, adjuvanted whole parasite vaccines, ready for pre-clinical testing. We will build on our previous experience with chemical tools to load whole parasites with adjuvants. To measure the potency of the new vaccines, we aim to measure early skin-based humoral and cellular immune markers which correlate with protection in our samples from prior and novel controlled human infection models. We will assess the functionality of antibodies by adapting our current molecular imaging tools to quantitatively analyze movement kinematics of parasites in representative 3D environments resembling the human skin. Cellular correlates of protection in skin will be mapped using imaging mass cytometry on freshly obtained skin biopsies from experimentally infected volunteers. Through combined, parallel analysis of circulating immune markers by high-dimensional flow cytometry, we aim to take a comprehensive approach including local and circulating markers to identify protective immune responses. This high-risk high-gain proposal is aimed to break the impasse in the field of parasite vaccine development and open a novel out-of-the-box avenue to fill the vaccine pipeline.

ERC Starting Grant 2021 – Anna Alemany – Deciphering signalling pathway dynamics during cell-fate commitment in stem cells

i-SignalTrace

Anna Alemany, PhD, Assistant Professor

Department of Anatomy & Embryology

• ERC Starting Grant 2021 – panel LS2
• EC contribution: EUR 1.500.000
• Start date: 01 March 2023 – End date: 29 February 2028

Abstract

Understanding the identity and intensity of the specific extracellular signals that a cell experiences at different times during its differentiation is essential to develop advanced cellular therapies. However, uncovering the sequence of these signaling events, their intensities, timing, and relevance in development and disease is proving to be very challenging.

Here, I propose to build i-SignalTrace: a CRISPR/Cas9-based molecular recorder with the capacity to store both lineage information and signalling pathway activity for multiple signals over time in single cells. By performing kinetic experiments and mathematical modeling, I will use i-SignalTrace to extract the probability of signalling pathways to be activated in stem cells when subject to different extracellular signals and reconstruct the lineage tree of pathway activities during differentiation with single-cell resolution. In combination with single-cell RNA sequencing, i-SignalTrace will make it possible to characterize transition and intermediate states along differentiation trajectories, and quantify the integration between extracellular signals and autonomous programs of gene expression. These results will allow predicting the differentiation trajectories that stem cells follow when subject to external perturbations, and deciphering the role of heterogeneity in signalling pathway activity during cell-fate commitment.

Using i-SignalTrace, I will identify missing or redundant signalling pathways induced during in vitro differentiation protocols. Therefore, I expect that exploitation of i-SignalTrace will allow establishing new criteria to design protocols to differentiate stem cells on demand. As a proof-of-concept, I propose a framework to improve the functionality of monolayer-derived cardiomyocytes. Taken together, i- SignalTrace will find applications in both fundamental developmental biology and translational regenerative medicine, which will benefit a much wider scientific community.

ERC Starting Grant 2020 – Baoxu Pang - The darker side of the genome: systemically studying the biology of repressive elements - silencers - in the human genome

Silencer

Baoxu Pang, PhD, Assistant Professor 
Department of Cell and Chemical Biology

• ERC Starting Grant 2020 - panel LS2
• EC contribution: EUR 1,750,000
• Start date: 01 February 2021 - End date: 31 January 2026

Abstract

Less than 1.5% of the human genome contains protein coding information of the estimated 25,000 genes. The rest of the non-coding genome includes many regulatory elements that control the spatial and temporal transcription of genes. With the help of the non-coding regulatory elements, the diverse cell types and tissues of a complex human body could be derived from the combinational expression of a limited number of genes from the same copy of the genome. Most regulatory elements (REs) have been characterized extensively, e.g. promoters, enhancers and insulators. These REs have been implicated to play very important roles in cell physiology, tissue development and disease onsets. Surprisingly, one class of REs—silencers—which repress the transcription of genes, have not been systematically characterized and studied. I have developed a lentiviral system to systematically identify functional silencer elements. In the small-scale proof-of-principle experiments, by focusing on the transcriptional factor (TF) accessible DNA sequences, I showed that this system is robust to identify novel and bona fide silencers, which could be validated using complementary functional assays such as luciferase and CRISPR knockout assays. In this proposed research plan, I aim to identify silencers in an unbiased way, rather than focusing on TF accessible regions, to have a more general understanding of the biology of silencers. Based on the unbiased identification of silencers, I aim to identify a general pattern of epigenetic modifications of silencers, unique combination of sequence motifs, responsible regulatory TFs, biological pathways that are regulated by silencers, diseases that might be related to mutations in silencers, and finally better manipulation strategies of silencers.

ERC Starting Grant 2019 – Noel de Miranda - RAtional design of canceR ImmunoTherapY: one size does not fit all

RARITY

Noel de Miranda, PhD
Department of Pathology

• ERC Starting Grant 2019 - panel LS7
• EC contribution: EUR 1,499,795
• Start date: 01 December 2019 - End date: 30 November 2024

Abstract

Checkpoint blockade immunotherapies have revolutionized cancer treatment. However, this immunotherapy only benefits a minority of patients (< 15%), mainly those diagnosed with cancers having many mutations. Furthermore, checkpoint blockade therapy does not selectively activate cancer-reactive T cells. RARITY responds to these shortcomings, aiming to provide innovative solutions for the development of effective immunotherapies for patients who do not benefit from current treatments. The ground-breaking preliminary data included in this application demonstrates that cancer-reactive T cells can be naturally present in so-called non-immunogenic cancers and that they acquire distinctive phenotypes. RARITY will apply state-of-the-art technologies to fingerprint these phenotypes. This will allow the isolation of cancer-reactive T cells from tumour tissues and their employment as highly-effective therapies. Therapeutic vaccination with cancer antigens can also be used to induce T cell responses in patients where natural activation of cancer-specific T cells is not detectable. However, the applicability of vaccination is compromised by the lack of specific targets, particularly in malignancies with few mutations. RARITY will address this problem by deploying a novel class of cancer antigens. An unprecedented screening of non-exomic genomic regions will be done to detect unannotated proteins that arise from de novo transcription and translation events. These proteins can then be targeted by personalized immunotherapies. Finally, thought-provoking findings included in RARITY suggest that immune cell subsets other than T cells play a major role in anti-tumour immune responses. These subsets need to be fully inventoried and categorised so that complementary strategies to T cell immunotherapies can be developed. RARITY will do so by conducting multidimensional analysis of cancer microenvironments using imaging mass cytometry and ex vivo modulation of immune responses.

ERC Starting Grant 2017 – Thom Sharp - Protein nano-patterning using DNA nanotechnology; control of surface-based immune system activation

BioNanoPattern

Thom Sharp, PhD, Tenure track researcher

Department of Molecular Cell Biology

• ERC Starting Grant 2017 - panel LS9
• EC contribution: EUR 1,499,850
• Start date: 1 January 2018 - End date: 31 December 2023

Abstract

Protein nanopatterning concerns the geometric arrangement of individual proteins with nanometre accuracy. It is becoming apparent that protein nanopatterns are essential for cellular function, and have roles in cell signalling and protection,phagocytosis and stem cell differentiation. Recent research indicates that our immune system is activated by nanopatterned antibody platforms, which initiate the classical Complement pathway by binding to the first component of Complement, the C1 complex. DNA nanotechnology can be used to form self-assembled nanoscale structures, which are ideal for use as templates to pattern proteins with specific geometries and nanometre accuracy. I propose to use DNA to nanopattern antigens and agonistic aptamers with defined geometry to study and control Complement pathway activation by the C1 complex. To develop and demonstrate the potential use of DNA to nanopattern proteins, the first aim of this proposal is to design DNA nanotemplates suitable for patterning antibody-binding sites. Antibodies and C1 will bind with specific geometry, and the relationship between antibody geometry and Complement activation will be assessed using novel liposome assays. Using DNA to mimic antigenic surfaces will enable high-resolution structure determination of DNA-antibody-C1 complexes, both in solution and on lipid bilayer surfaces, using phase plate cryo-electron microscopy to elucidate the structure-activation relationship of C1. The second aim of this proposal is to evolve agonistic aptamers that directly bind to and activate C1, and incorporate these into DNA nanotemplates. These nanopatterned aptamers will enable further study of C1 activation, and allow direct targeting of Complement activation to specific cells within a population of cell types to demonstrate targeted cell killing. This may open up new and highly efficient ways to activate our immune system in vivo, with potential for targeted anti-tumour immunotherapies.

ERC Starting Grant 2016 – Annette van der Helm van Mil - Rheumatoid Arthritis Caught Early: investigating biological mechanisms preceding chronification of joint inflammation to identify patients prior to presentation of classic chronic arthritis

RACE

Prof. Annette van der Helm – van Mil, MD, PhD 
Department of Rheumatology

• ERC Starting Grant 2016 - panel LS7
• EC contribution: EUR 1,500,000
• Start date: 01 October 2017 - End date: 31 March 2024

Abstract

Rheumatoid Arthritis (RA) causes long lasting disability. At the time of clinically evident arthritis and diagnosis, the disease is already persisting, requiring long-term suppressive treatment. My overarching aim is to prevent chronic arthritis and RA by inhibiting the evolving auto-immune response in a pre-arthritis phase. Currently, identification of RA-patients before the classic presentation with clinically evident chronic arthritis is beyond the state of the art. I here aim to achieve this early recognition by increasing the mechanistic understanding of pre-arthritis phases. I intend to study RA-specific auto-immune responses at the cellular and humoral level as well as markers reflecting local and systemic inflammation. These aspects are selected based on my world-wide validated rule to predict RA-development in early arthritis and on recent work on progression from Clinically Suspect Arthralgia (CSA) to clinical arthritis. This project is now finally feasible, thanks to unique ‘pre-RA’ cohorts and cross-boundary preparatory work done with basic scientists, clinicians and engineers. My research concept is to integrate the products of separate trajectories in a longitudinal study and translate it to the clinic. Patients with CSA will be studied serially in time. Using validated methods and novel techniques and insights we will: delineate molecular and predictive features of RA-specific auto-antibodies and auto-antibody secreting B-cells, identify improved markers of systemic inflammation and test and validate a computer-aided image analysis system to detect subclinical joint inflammation on MRI. Serial data will be combined to reveal interactions between markers and time relationships. Lastly a prediction model identifying imminent RA will be developed. The forefront position of my group allows national and international validation. Together, this multidisciplinary and intersectorial project will open new horizons for preventive, targeted interventions.

ERC Proof-of-Concept Grant 2023

Baoxu Pang - Targeting the dark side of the human genome — non-coding regulatory elements — to treat diseases

Project acronym: TargetNCREs

PI: Baoxu Pang, PhD
Department of Cell and Chemical Biology

• EC contribution: EUR 150.000
• Start date: 01 May 2024 – End date: 31 October 2025

Abstract: will follow soon