KU Leuven

PhD on Food-induced duodenal immune activation

2024-07-05 (Europe/Brussels)
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KU Leuven is an autonomous university. It was founded in 1425. It was born of and has grown within the Catholic tradition.

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TARGID, the translational research center for gastrointestinal disorders, is one of the largest research groups in KULeuven Biomedical Sciences and is a leading gastrointestinal research center on a global level. The Gastrointestinal Motility and Sensitivity Research group focuses on research in patients and healthy controls, to understand the pathophysiology, impact and treatment of chronic gastrointestinal symptoms, as present in patients with Disorders of Gut-Brain Interaction. This comprises the irritable bowel syndrome and functional dyspepsia, as well as gastroparesis and many similar highly prevalent conditions. The group is led by Prof. J. Tack and comprises 15 to 20 researchers from varied backgrounds. Dr. Florencia Carbone is a research leader in the group and Dr. Karen Van den Houte is a postdoctoral researcher. Given the international composition of the group, the language for daily interactions is mostly English.
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Project

The Gastrointestinal Motility and Sensitivity Group at the University of Leuven (KU Leuven, Belgium) is looking for a highly motivated PhD student to unravel the cellular and molecular mechanisms underlying food reactivity and response to dietary and anti-inflammatory therapy in patients with Functional Dyspepsia (FD).

FD affects 7.2% of the adult population and has a significant impact on quality of life. Patients present with recurrent symptoms in the stomach region, but routine investigations including endoscopy are macroscopically normal. Recent studies have shown low-grade duodenal inflammation characterized by influx of activated eosinophils and mast cells and impaired mucosal barrier function in FD. We hypothesize that symptoms are triggered by specific food allergens which, in the presence of impaired mucosal barrier, activate mast cells and eosinophils. Two ongoing pivotal trials are investigating this hypothesis. In a placebo-controlled trial, we are investigating the effects of the endogenous mast cell stabilizing agent palmitoylethanolamide on symptoms and duodenal mucosal alterations in FD patients. In a sham-controlled dietary elimination trial in patients without classical IgE-mediated food alleriges, we are studying the effect of elimination of trigger nutrients, identified by duodenal confocal laser endomicroscopic evaluation of atypical food allergies, on symptoms and duodenal mucosal alterations in FD patients. In all patients, duodenal biopsies and serum samples for various assessments were obtained at baseline and at the end of medical or dietary therapy. In addition, comparator samples are available from healthy controls.

The PhD fellow will be involved in sample collection and some logistics for the studies, which are run by a clinically focused PhD fellow. The aim of your part of the project is to use these samples and ongoing and follow-up in vivo studies to understand:

1) The molecular basis of the alterations of integrity of the duodenal mucosa in FD patients and its evolution during medical and dietary therapy.

2) The characterisation of the cellular inflammatory infiltrate in FD patients and its evolution during medical and dietary therapy.

3) The pathway through which IgE-negative patients display acute atypical allergic reactions to food components as evaluated by duodenal confocal endomicroscopic studies. Both mast cell targeting as eosinophil targeting mechanisms will be considered.

The hypothesis focuses on non-IgE mediated mast cell activation, through for instance MRGPRX2 receptor activation.

4) The findings in the palmitoylethanolamide study will be correlated with tissue levels of palmitoylethanolamide and their correlation with markers of mast cell activation and response to therapy.

5) There is a potential to correlate mechanistic observations to a genetics database.

Key references:

1. Sperber A, Bangdiwala SI, Drossman DA, Ghoshal UC, Simren M, Tack J, Whitehead W, et al. Worldwide Prevalence and Burden of Functional Gastrointestinal Disorders, Results of Rome

Foundation Global Study. Gastroenterology 2021;160: 99-114.

2. Sarnelli G, Pesce M, Seguella L, Lu J, Efficie E, Tack J, De Palma FDE, D’Alessandro A and Esposito G. Impaired Duodenal Palmitoylethanolamide Release Underlies Acid-Induced Mast Cell

Activation in Functional Dyspepsia. Cell Mol Gastroenterol Hepatol. 2020; 11: 841-855.

3. Fritscher-Ravens A, Schuppan D, Ellrichmann M, Schoch S, Rocken C, Brasch J, Bethge J, Bottner M, Klose J and Milla PJ.. Confocal endomicroscopy shows food-associated changes in the

intestinal mucosa of patients with irritable bowel syndrome. Gastroenterology 2014;147.

4. Van den Houte K, Bercik P, Simren M, Tack J, Vanner S. Mechanisms underlying food-triggered symptoms in disorders of gut-brain interactions. Am J Gastroenterol. 2022 Jun 1;117(6):937-946

5. Schol J et al. Role of atypical food allergies in functional dyspepsia: evaluation by six food elimination diet and confocal laser endomicroscopy food allergy testing. Gastroenterology

2022; 162: S926.

6. Giancola F, Volta U, Repossi R, Latorre R, Beeckmans D, Carbone F, Van den Houte K, Bianco F, Bonora E, Gori A, Costanzini A, Boschetti E, Caio G, Vanuytsel T, Stanghellini V, Tack J and De

GIiorgio R. Mast cell-nerve interactions correlate with bloating and abdominal pain severity in patients with non-celiac gluten / wheat sensitivity. Neurogastroenterol Motil. 2020; 32: e13814.

Profile

  • You hold a Master’s degree in Biomedical Sciences, Bioengineering, Biotechnology, or a related discipline.
  • Hands-on experience with biochemical assays such as Western blot and qRT-PCR analysis, FISH, cell culture, immunohistochemistry, etc. is a strength. 
  • You have a strongh scientific curiosity, are motivated for research, can cope with the need for problem solving as research evolves, and display great precision in your work. You are able to function independently as well as in team. You can interact with patients and patient sample collection. 
  • You have excellent oral and written communication skills in English.

Offer

  • We offer a PhD position in a young and dynamic team within an excellent working environment.
  • You will have the opportunity to work on high impact projects in a multidisciplinary environment with access to state-of-the-art technologies and infrastructure.
  • We support PhD students with excellent (daily) guidance and training, and provide the opportunity to participate in (inter)national collaborations and conferences. We aspire to create a lab culture where all talents can flourish and feel welcome, regardless of age, race, gender, cultural background, or disability.
  • The KU Leuven has a strong international character and is located in Leuven, close to Brussels at the heart of Europe.

Interested?

For more information please contact Prof. dr. Jan Tack, tel.: +32 16 37 74 74, mail: jan.tack@kuleuven.be or Mrs. Maria Florencia Carbone, mail: florencia.carbone@uzleuven.be.

KU Leuven strives for an inclusive, respectful and socially safe environment. We embrace diversity among individuals and groups as an asset. Open dialogue and differences in perspective are essential for an ambitious research and educational environment. In our commitment to equal opportunity, we recognize the consequences of historical inequalities. We do not accept any form of discrimination based on, but not limited to, gender identity and expression, sexual orientation, age, ethnic or national background, skin colour, religious and philosophical diversity, neurodivergence, employment disability, health, or socioeconomic status. For questions about accessibility or support offered, we are happy to assist you at this email address.

Dettagli del lavoro

Titolo
PhD on Food-induced duodenal immune activation
Datore di lavoro
Sede
Oude Markt 13 Lovanio, Belgio
Pubblicato
2024-05-02
Scadenza candidatura
2024-07-05 23:59 (Europe/Brussels)
2024-07-05 23:59 (CET)
Tipo di lavoro
Salva lavoro

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Informazioni sul datore di lavoro

KU Leuven is an autonomous university. It was founded in 1425. It was born of and has grown within the Catholic tradition.

Visita la pagina del datore di lavoro

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