Call for Applications Spring

Main supervisor: Adj. Professor Carlos Rogerio Figueiredo, Institute of Biomedicine, University of Turku
crdefi@utu.fi 

Research group website:
https://www.miorg.fi  

Other supervisor(s): Professor Menashe Bar-Eli, MD Anderson Cancer Centre, University of Texas, USA
Website: https://faculty.mdanderson.org/profiles/menashe_bar-eli.html 

Pilot project description 

In cancer immunity, dendritic cells (DCs) are essential for the priming and generation of antitumor T cells that target tumors. Our latest review dissects the nature of desert tumors, known for their severe absence of antitumor T cells. Moreover, we demonstrated how desert tumors dispose of several molecular features to suppress local immunogenicity despite their mutational load. Disrupting immunogenic cell DCs impairs anti-tumor immunity and increases resistance to current immune checkpoint therapies (ICT), such as anti-PD1 blockade.  

One prominent way of disrupting DC’s ability to prime T lymphocytes, specifically, cytotoxic T cells is by damping their ability to process and present antigens through MHC-I molecule. Studies are focusing on uncovering novel molecules and pathways that could boost DCs immunogenicity within the tumor microenvironment (TME). On this front, the immunoproteasome, a specialized protease complex, is critically important for shaping the diversity of cancer antigens (immunopeptidome), essential for robust antitumor immune responses. This diversity can facilitate the priming and generation of new antitumor T cells. When tumor signals disrupt immunoproteasome functions, T cell generation drops, weakening cancer immunity and consequent responses to cancer immunotherapies, such as anti-PD1 blockade.  

The Medical Immuno-Oncology Research Group (MIORG) at the University of Turku has uncovered a novel autocrine immune factor produced by DCs. This factor is key to activating the immunoproteasome, which in turn boosts antigen processing and MHC-I expression on DCs for better T cell priming. In this project, we are investigating how the deficiency in this factor negatively impacts the immune landscape of skin melanoma. We also aim to validate approaches that increase its levels in DCs, boosting T cell generation in combination with anti-PD1 therapy, laying the rationale for future development of new combinatorial immunotherapies.

Keywords: Immune Checkpoint Therapy; Cancer; Immunoproteasome; Cold Tumors; anti-PD1; cross-presentation; Innate Immunity 

Main supervisor: Jyrki Heino,  M.D., Ph.D., professor, department head, Department of Life Technologies, University of Turku

Other supervisor(s):
Veli–Matti Kähäri, M.D., Ph.D., professor and chief physician, Department of Dermatology, University of Turku and Turku University Hospital
Pilvi Riihilä, M.D., Ph.D., Docent, Department of Dermatology, University of Turku and Turku University Hospital
Liisa Nissinen, Ph.D., Docent, FICANWest Cancer Research Laboratory, University of Turku and Turku University Hospital
Pekka Rappu, Ph.D., Docent, Department of Life Technologies, University of Turku
Elina Siljamäki, Ph.D., Docent, Department of Life Technologies, University of Turku

Pilot project description:

Malignant tumours consist of transformed cancer cells, and of numerous other cell types including cancer associated fibroblasts (CAFs), tumour associated macrophages (TAMs), neutrophils, lymphocytes and endothelial cells. All cell types regulate each others’ phenotype and behaviour and cancer progression. Extracellular matrix (ECM) – mainly produced by CAFs – is an important component of tumour microenvironment. ECM has major impact on cancer cells, on the efficacy of immunotherapies and finally on the disease outcome.

We have developed new 3D spheroid based methods to study the interactions of different cell types: human cutaneous squamous cellular carcinoma (cSCC) cells, CAFs and TAMs/neutrophils. Using e.g. mass spectrometry, RNA-sequencing, microscopy and cellular assays for proliferation, phenotype/plasticity and invasion the project aims to unveil the TAM and neutrophil based regulatory mechanisms of invasion and ECM remodelling. Furthermore, our preliminary results have revealed the remarkable plasticity of TAMs. The project aims to find molecular mechanisms used by CAFs and cSCC cells to regulate TAM phenotype.

In our recent paper we showed that spheroid model can be used to successfully screen potential drug molecules (Siljamäki et al., Oncogene, 2023). In this project the spheroids containing three different cell types will be used to test the effects of the inhibitors of critical signalling pathways. The model also allows to test putative drug molecules targeted to macrophages and neutrophils.

Finally, we have recently established a method to combine laser capture microscopy to mass spectrometry and shown that it is possible to get detailed information about e.g. ECM composition in different tumour areas of paraffin embedded SCC tumours and their metastases. This in vivo information is critical for interpretation of the results from in vitro experiments focused on the effects of macrophages and neutrophils on the composition and organization of ECM. (1998 / 2000)

Key words: Macrophage, Neutrophil, Fibroblast, Tumor stroma, Extracellular matrix, Drug development

Main supervisor: Adj Prof. Maija Hollmén, Medicity Research Facility and InFLAMES Flagship
https://hollmenlab.com/

Other supervisor(s): Prof. Sirpa Jalkanen, Medicity Research Facility and InFLAMES Flagship 

Pilot project description:

The precise therapeutic control of myeloid malignancies and cancer-driven immune dysfunction remains a critically unmet challenge that has not been successfully addressed with the current arsenal of drugs. Targeting Clever-1, a scavenger receptor expressed by both immunosuppressive macrophage populations and myeloid leukemia cells presents a way to kill two birds with one stone. As such, an antibody targeting Clever-1 (bexmarilimab) is currently under investigation in the BEXMAB phase I/II trial in combination with standard of care, azacytidine, in acute myeloid leukemia and myelodysplastic syndrome.

In this project, we will integrate concurrent efficacy data, obtained from the BEXMAB trial, and detailed molecular level information about bexmarilimab’s mechanism-of-action by single-cell RNA sequencing of patient bone marrow samples before and after treatment. We will also implement mouse models of chemotherapy-induced leukopenia to study Clever-1–regulated hematopoietic recovery, a phenomenon observed in BEXMAB patients after bexmarilimab administration. Altogether, this project aims to understand the homeostatic functions of Clever-1 in the bone marrow and to improve the clinical outcome of patients with myeloid leukemias.

The study is performed in Medicity Research Laboratory at the University of Turku. The applicant should have good knowledge in animal experimentation, multicolor flow cytometry and be proficient in using R.

Key word(s): hematopoiesis, leukemia, macrophages, mouse models, sc-RNAseq, clinical trial

Main supervisor: Arno Hänninen, University of Turku, Turku University Hospital, InFLAMES Flagship

Other supervisor(s): Tapio Lönnberg, Turku Bioscience Centre and InFLAMES Flagship,
University of Turku
https://bioscience.fi/research/single-cell-genomics-immunology/profile/

Pilot project description

As the core of a clinical follow-up study, we profile systemic lupus erythematosus (SLE) patients’ immune system by novel approaches. SLE is a systemic autoimmune disease with great variation in its clinical course. New biomarkers are required for better prediction of each individual’s risk of developing organ involvement and activity bursts (flares). SLE often leads to coronary heart disease, chronic lung disease, chronic kidney disease, skin and joint involvement and other morbidities.

Myeloid cells and B-lymphocytes have important roles in SLE pathogenesis. Myeloid cells secrete mediators and B-cells produce autoantibodies to induce inflammation. We use a broad panel of immunological tests to profile B-cell subsets and monitor neutrophil and monocyte phenotypes and activity, and determine the presence of microorganisms in white blood cells. Our hypothesis is that microorganisms derived from the gut or mucosal surfaces act as triggers of inflammation and autoantigen release. We further hypothesize that individual differences in immune receptor signaling due to intrinsic factors and environmental adaptation determine this activity, reflected on the level of individual gene expression. Therefore, we study individual variation in monocytes’ and B-cells’ responses to microbial encounters using mimics of microbial encounters. To identify individual tuning of immune response on the level of single genes, we study each individual’s myeloid cells and B-lymphocytes using single-cell transcriptomics (scRNA-seq) and combine it with extended immunological profiling and clinical data. This may lead to identification of novel biomarkers related to individual variance in immune responsiveness and help stratify SLE patients for justification of individual treatment decisions.

This study involves University of Turku, Turku Biosciences and the diagnostic laboratory and rheumatology unit of Turku university hospital. Both supervisors are affiliated in InFLAMES and collaborate in this project.

Key words: Systemic lupus erythematosus (SLE); novel biomarkers for prediction; myeloid cells and B–lymphocytes; TLR–ligands; single–cell RNA sequencing; 16S RNA sequencing

Main supervisor: Sirpa Jalkanen, Director, InFLAMES Flagship

Other supervisor(s): Adj Prof. Maija Hollmén, Medicity Research Facility and InFLAMES Flagship https://hollmenlab.com/

Pilot project description:

We are interested in those multiple ways cancer modifies our immune system for boosting its own growth and spread. The project is based on our recent finding that breast cancer causes significant changes in the draining lymph nodes, which promote their metastasis. Using single cell sequencing of metastatic lymph nodes of breast cancer patients, we have found several immune-related hit molecules, the expression of which is drastically changed in metastatic lymph nodes when compared to non-metastatic ones. This project aims at analyzing 1) the expression of these hit molecules at the protein level in different breast cancer types, 2) association of their expression to the immune landscape of the tumors, 3) correlation of the expression to clinical parameters 4) whether the soluble forms of the selected hits can be used as diagnostic/prognostic biomarkers. The project is expected to provide new targets for diagnosing and preventing metastasis of cancer cells and the modulation of anti-tumor immunity. The project will be performed in MediCity at University of Turku in close collaboration with clinicians. The project utilizes unique human materials and several technologies such as multiplex immunohistochemistry and most modern imaging tools, flow cytometry, ELISA and bioinformatics.

Key word: lymphatics, immune landscape, cancer

Main supervisor: Laura Kakkola, Institute of Biomedicine, University of Turku

Other supervisor(s): Ilkka Julkunen, Institute of Biomedicine, University of Turku

Pilot project description:

The aim of this project is to reveal the innate immune responses that seasonal influenza viruses A/H1N1pdm09 from years 2009 to 2024 and avian influenza viruses from years 2022-2023 induce or inhibit in infected cells. With this information, we aim to analyze the mechanisms of adaptation of influenza viruses to replication in human cells. The role of the major viral innate immune repressor, NS1, in adapted influenza viruses will be studied in detail. We expect to find differences in the adapted influenza viruses and in the ability of NS1 proteins to inhibit innate immune pathways. Further, the hemagglutin directed antibodies will be analyzed for a possible cross-reactivity in animals and humans. This project will give significant information on the immune responses and adaptation process of influenza viruses, especially of avian influenza viruses currently causing a global threat.

The project will be conducted in the Institute of Biomedicine, Faculty of Medicine. In the project you will use live pathogenic viruses and cloned virus genes, set up novel mass cytometry methods and use cell culture, elisa, RT-qPCR, protein production methods and data analysis (GraphPad, Excel, FlowJo, etc.). You will gain specific expertise to work in biosafety level 3 laboratory, the skill that is directly transferable to the e.g. clean room work in pharmaceutical companies. The successful candidate has to be able to work with pathogenic viruses in biosafety level 3 laboratory, i.e. passing of thorough health check and official security clearance is required.

Key words: influenza virus, avian influenza, innate immunity

Main supervisor: Riitta Lahesmaa, MD, PhD, Professor of Systems Immunology, Director, Turku Bioscience Centre and InFLAMES Flagship

Other supervisor(s): Tanja Buchacher, PhD, Senior Researcher
https://bioscience.fi/research/molecular-systems-immunology/profile/

Pilot project description:

Regulatory T cells (Treg) are vital for maintaining immune tolerance and immune homeostasis. Modulating their function has significant therapeutic potential for controlling human autoimmune and inflammatory diseases as well as cancer. In spite of advances in Treg cell biology, the molecular mechanisms of human Treg differentiation and function are incompletely understood.

The Lahesmaa group identifies new ways to control Treg. We have discovered novel factors upregulated in Tregs. This project will study the role of two such factors in regulating Treg differentiation and function. We have already shown they both influence expression of FOXP3, a key transcription factor defining Treg and that one of them is upregulated in tumor infiltrating lymphocytes. These along with our other preliminary data demonstrate feasibility and notably highlight these two factors as highly interesting novel regulators of Treg response.

The work is done in Lahesmaa lab at Turku Bioscience Centre with an excellent research infrastructure. The doctoral researcher will study clinical samples from patients with immune mediated diseases and cancer and use a range of cutting-edge methods in molecular and cellular biology, epigenetics and bioinformatics including RNAi/LNA mediated silencing/CRISPR-Cas9 gene editing combined with single-cell RNA-seq, mass cytometry and proteomics. All the methods are optimized in the group as reported (Buchacher et al. 2023 doi: 10.1016/j.celrep.2023.113469; Shetty et al. 2022 doi: 10.1093/nar/gkac256; Khan et al. 2022 doi: 10.1016/j.crimmu.2020.02.001; Andrabi et al. 2023 doi: 10.1016/j.imlet.2023.09.001).

The results are expected to provide new insights and basis for developing new strategies for novel targeted therapies for autoimmune and inflammatory diseases and cancer.

The PhD training provides the candidate with in-depth understanding of central principles in the control of human immune response – valuable for a career both in industry and academia.

Key words: Human immune response, T cells, regulatory T cells, immune mediated diseases

Main supervisor: Urpo Lamminmäki, PhD, prof., Department of Life Technologies / Biotechnology, University of Turku
https://antibodyengineering.utu.fi/

Other supervisor(s):
Bryce Nelson, PhD, Head of Antibody Engineering, Orion Pharma Oy, Turku, bryce.nelson@orionpharma.com
https://www.orion.fi/
Antti Kulmala, PhD, Senior Scientist, Orion Pharma Oy, Turku,
antti.kulmala@orionpharma.com,
https://www.orion.fi/

Pilot project description:

This collaborative project between Dept. of Life Technologies/UTU and Orion Oy aims to establish aversatile technology platform to advance development of next-generation immunotherapeutics. With >170 clinically approved antibody drugs, antibodies stand as a major triumph in modern medicine. Today, scientists are striving to pioneer immunotherapies based on increasingly intricate designs like bispecific antibodies, posing significant challenges in their development. Single heavy chain variable domains (VHHs), presenting the smallest antigen binding units from immunoglobulins, hold great potential as simple molecular components for crafting future biotherapeutics.

Project’s key goals are: i) to create of a universal molecular library for rapid discovery of novel VHHs to various disease targets, ii) to demonstrate benefits of these VHHs in intricate antibody designs. As the VHH framework is extracted from its natural environment within the intact antibody, it needs to be optimized for biophysical characteristics, such as stability and solubility. Here, an iterative engineering process using bioinformatics-based structural design and directed evolution is applied to explore different solutions to create a human VHH domain with superior biophysical characteristics, followed by diversification of the binding site by emulating natural immunoglobulin diversity.

Resulting preliminary VHH libraries will be filtered with phage and mammalian cell display techniques to eliminate potentially problematic protein variants. The final highly diverse phage display VHH library will be validated by selecting VHH binders to relevant immunotherapy targets, incorporating the VHHs in different bi- and multispecific antibody designs, followed by careful analysis of their biochemical/-physical and biological properties. The technology platform developed here is expected have a considerable impact on the possibilities to investigate and develop next-generation immunotherapeutics in Finland.

Key words: Antibody engineering, Antibody library, Next-generation biotherapeutics, VHH

Main supervisor: Pieta Mattila, PhD, Title of Docent, InFLAMES research Flagship, Institute of Biomedicine, University of Turku

Group website: https://mattilalab.utu.fi/

Other supervisor(s): Saara Hämälistö, PhD, FICAN West, Institute of Biomedicine, University of Turku

Group website: https://hamalistolab.utu.fi/

Pilot project description:

B cells form a vital branch of the adaptive immune system by mounting antibody responses and immunological memory. Antigen binding to the B cell antigen receptor (BCR) triggers a branched signaling network with complex cell biological outcomes enabling the launch of antibody responses. In this project, based on our strong ongoing research, we focus on the roles of the secreted extracellular vesicles (EVs), together with intracellular lysosomes, as novel regulators of B cell activation and immune response.

A) B cell-derived EVs (B-EVs) in modulation of the immune system. Hypothesis: Via robust secretion of EVs, B cells modulate their cellular environment and immunological status.

EVs have lately emerged as a powerful layer of intercellular communication by transmitting biological cargo, like enzymes, regulatory RNAs and lipids, to the recipient cells. Our ongoing work has revealed highly interesting characteristics of B-EVs that the candidate will study further focusing on the lead molecules identified in the proteomic and transcriptomic profiling. By injecting labelled B-EVs into the mouse, they will examine the targeting of B-EVs in tissues and the effects the EVs induce in the recipient cells, the homeostasis of the immune system, and mounting of the immune response.

B) Lysosomes in B cell activation. Hypothesis: Lysosomes play a previously unrecognized role in regulating early events in B cell activation.

In our ongoing research we have found that inhibition of lysosomes strongly impairs B cell activation. The candidate will participate in research unveiling the molecular mechanisms of this highly interesting acute role of lysosomes, and its functional impact in, e.g. vesicle release and antigen presentation.

This project, at the Institute of Biomedicine, University of Turku, utilizes e.g. advanced microscopy and flow cytometry and, as model systems, cultured cells and mice. Two research lines mitigate the risk and provide flexibility.

Key words: B cells, lymphocyte activation, antibody response, antigen signaling, lysosomes, extracellular vesicles

Main supervisor: Associate Professor Alexander Mildner, PhD, Department of
Biomedicine, InFLAMES Flagship
https://mildnerlab.utu.fi/

Other supervisor(s): Akira Takeda, PhD, Department on Biomedicine, InFLAMES Flagship
https://takedalab.utu.fi/

Pilot project description:

Tissue macrophages (M φ) have distinct functions based on their environment. For instance, lung alveolar Mφs (AMs) eliminate surfactant lipids. AMs acquire this ability from lung epithelial cells that release GM-CSF, which activates the lipid-handling transcription factor PPARg. However, PPARg comes in two isoforms, and previous studies have shown that PPARg2 is mainly found in adipocytes while PPARg1 is expressed in many cell types. In contrary, we found that PPARg2 and not PPARg1 is the primary isoform that grants lipid-degrading abilities to AMs, while other Mφs, such as splenic Mφs, only express PPARg1 (PMID: 36112694). Interestingly, a recent study suggests that the development of spleen Mφs is blocked in PPARg-deficient mice (PMID: 33765133). These results indicate that PPARg1 and PPARg2 are differentially regulated and play different roles in various Mφ subsets. We therefore speculate that PPARg2 is primarily involved in AMs lipid degradation, whilePPARg1 regulates a different set of target genes that are crucial for spleen Mφ differentiation. Since PPARg has emerged as a promising target in a multitude of pathologies like diabetes or pulmonary alveolar proteinosis, a better understanding of the isoform-specific functions and regulation of PPARg might contribute to develop more effective and targeted treatments.

In this basic immunological project, we aim to unravel the regulation and function of the PPARg isoforms 1 and 2 in lung and spleen Mφs, which can provide meaningful insights for more targeted drug development. We will use epigenetics (ChIP-Seq, Cut&Run, ATAC-Seq), molecular analysis (RNA-Seq, scRNA-Seq), Immunoblotting and specific, established PPARg1 and PPARg2 knockout mouse models under steady state conditions to identify PPARg1 and 2 function and their specific target genes. The research will be conducted in the Mildner lab, Department of Biomedicine, BioCity. All molecular techniques are established.

Key words: innate immunity, macrophage, epigenetics, differentiation

Main supervisor: Teemu Niiranen, MD, PhD, Professor, Department of Internal Medicine, University of Turku
https://www.hypertensioncenter.org

Other supervisor(s): Joonatan Palmu, MD, PhD, Department of Internal Medicine, University of Turku, jjmpal@utu.fi
https://www.hypertensioncenter.org

Pilot project description:

This is a dry lab/computational position for a PhD student interested in computational biology and microbiome analysis. The suitable candidate has a background in biostatistics, medicine, bioinformatics, epidemiology, computer science, biology, or mathematics. Professor Teemu Niiranen’s group (Internal Medicine Unit, Department of Clinical Medicine) works on a wide range of topics with a current focus on multi-omics analysis in large-scale population cohorts.

This overarching goal of the current project is to elucidate the role of the gut microbiome as a risk factor for systemic inflammation and incident autoimmune disease. The current research will be performed using data from the nationwide, prospective FINRISK 2002 cohort.

In the year 2002, over N=7200 FINRISK 2002 participants underwent a health examination, blood sampling and stool sampling. The participants have been followed up for over 20 years for incident health events. The stool samples have later been sequenced using shotgun metagenome sequencing, allowing us to comprehensively assess the gut microbiome of the participants. In addition, a panel of 45 circulating cytokines, including pro-inflammatory interleukins, chemokines and growth factors, has been measured in a subsample of N=3000 participants.

Our specific aims are:
1) To assess the cross-sectional associations between the gut microbiome and circulating cytokines.
2) To examine the prospective links between baseline gut microbiome and incident rheumatic autoimmune
disease (e.g. rheumatoid arthritis, systemic inflammatory disease) over a 20-year follow-up.
3) To study the prospective associations between the gut microbiome and incident inflammatory bowel
disease (Crohn’s disease and ulcerative colitis) over a 20-year follow-up.

We hypothesize that we will be able to discover numerous microbial signatures that are related to inflammation and autoimmune disease. Manipulation of the gut microbiome could provide potential novel therapies for these disorders.

Key words: Gut microbiome, immunology, inflammatory autoimmune disease

Main supervisor: Tero Soukka, PhD, Professor, Biotechnology, Department of Life Technologies, University of Turku
https://fi.linkedin.com/in/tero-soukka-4835bb2
https://research.utu.fi/converis/portal/detail/Person/794864

Other supervisor(s):
Alice Ylikoski, PhD, Senior Manager, Assay Technology, Radiometer Turku Oy;
Adjunct Professor (Docent), Nucleic Acid Analytics; Tampere University
alice.ylikoski@radiometer.fi
https://fi.linkedin.com/in/alice-ylikoski-34679530
Satu Lahtinen, DSc (Tech), University Lecturer, Biotechnology, Department of Life Technologies, University of Turku
https://fi.linkedin.com/in/satu-lahtinen-137196134

Pilot project description:

Technologies enabling higher binding capacity and antibody reactivity on solid-phase surfaces are needed to develop more rapid and sensitive immunoassays applicable in point-of-care testing and acute care immunodiagnostics for detection of biomarkers in different disease conditions, such as cardiac complications, infection and sepsis.

The objective of the proposed pilot project is to study construction of three-dimensional streptavidin base layer as generic solution for high capacity immobilisation of biotinylated antibodies on polystyrene microwells. The hypothesis is that using streptavidin conjugates of flexible polymers, adsorbed either directly on the polystyrene surface, or through strongly adsorbed anchor proteins, not only high biotin binding capacity, but also high reactivity of immobilized biotinylated antibodies can be achieved. The high surface density of antibodies and their flexible coupling in the three-dimensional layer should result in accelerated binding kinetics when the diffusion limitations are removed. The rapid binding kinetics further facilitates improved sensitivity when the non-specific binding on the surface is under control.

The project plan of the study has two main subobjectives: 1) Construction of streptavidin polymer conjugates, their immobilization on microwells both directly and via anchor protein to form three-dimensional streptavidin surfaces, and characterization of the biotin and biotinylated antibody binding capacity and stability of the produced surfaces. 2) Evaluation of the immunoassay performance, including assay kinetics, sensitivity and dynamic range with a model biomarker, using the most promising candidates of the produced surfaces as base layers for immobilization of the biotinylated antibodies.

This study is carried out at Biotechnology unit in intended collaboration (e.g., co-supervision, reagent support, visit to company) with Radiometer Turku Oy, which develops and manufactures immunoassays for acute care diagnostics.

Key words: Immunodiagnostics, point–of–care testing, streptavidin, antibody immobilization, protein adsorption

Main supervisor: Jorma Toppari, Professor, MD, PhD, Institute of Biomedicine, DIPP research

Other supervisor(s): Mari Vähä–Mäkilä, Institute of Biomedicine, DIPP–research group

Pilot project description:

Join the ImmuDocs project, where we are dedicated to advancing our understanding of Type 1 Diabetes (T1D). In 2021, T1D affected 8.4 million globally, with projections estimating 13.5–17.4 million cases by 2040. Most autoimmune diseases, including T1D, lack a cure due to complexity and incomplete understanding of their underlying mechanisms. Treatments focus on symptom management and immune system activity reduction, highlighting the urgent need for ongoing research and more effective therapies.

Our project in the DIPP research centre aims to investigate the transcriptome and epigenome of peripheral mononuclear blood cells related to T1D, leveraging data collected from the PAMP (Pathogen Associated Molecular Patterns) and DIPP (The Finnish Type 1 Prediction and Prevention) studies. Led by a multidisciplinary team of experts, including immunologists, bioinformaticians, and pediatric endocrinologists, the research seeks to uncover critical insights into the immunoregulation process during the presymptomatic phase of T1D. Using advanced methods, like RNA sequencing and RRBS, we analyze samples collected over the years from children developing T1D. Our unique longitudinal case-control study, coupled with an ex vivo cell model, focuses on screening human innate immune pathways. In this project, you will study a small part of the 17000 samples collected since 2010, including 3700 from children progressing to T1D. The project’s case-control pairs have already been formed, and samples have been selected and sequenced. The ideal candidate for studying epigenome and transcriptome would possess a molecular biology and genetics foundation, bioinformatics skills for data analysis, statistical knowledge for interpretation, critical thinking abilities, and effective communication and collaboration skills. Our goal is to identify targets for new therapies and better ways to diagnose T1D. Join us in our mission to make a difference in the fight against T1D.

Key words: Innate immunity, macrophages, Type 1 diabetes, transcriptome, epigenome