ALLPret: Allergenicity Prediction Toolbox for novel foods
The EC funded Horizon Europe Marie Curie Doctoral Training Network ALLPreT project is an international PhD programme on new approaches, tools, and assays to enable the safe introduction of novel foods and protect humans from unacceptable food allergy risks coordinated by the University Medical Center Utrecht (UMCU). Together with 9 academic and 12 associated partners including industry partners across EU and US, it offers a unique opportunity to excellent Ph.D candidates (early stage researchers, ESRs) to gain experience and skills with short-term selected secondments within a world class consortium.
The ALLPreT project:
Introducing novel foods, such as insects, will contribute to the security and sustainability of European and global food supplies. However, these novel foods need to be safe (EU regulation 2015/2283). Determining the allergenic potential of food proteins is essential to the safety assessment of novel foods. Unfortunately, current methods to assess de novo allergenicity lack predictive power and are not validated. Consequently, food producers and risk assessors struggle with allergenicity assessment, slowing down the introduction of novel foods in our food supply. Enabling the safe introduction of novel foods, while protecting humans from unacceptable food allergy risks, calls for a multidisciplinary approach.
The ALLPreT Doctoral Training Network consists of a multidisciplinary group of researchers from The Netherlands, Austria, Germany, France, Luxembourg, Serbia, Denmark, and Bulgaria, aiming to discover new approaches, tools, and assays to enable the safe introduction of novel foods and protect humans from unacceptable food allergy risks. This will be done by unravelling food allergy mechanisms (e.g., route of sensitization (oral, respiratory and skin), involvement immune cells, in vitro/ in vivo responses), investigate intrinsic properties of allergenic proteins (e.g., epitopes, digestibility, physicochemical properties) and exploring the use of a threshold of sensitization.
ALLPreT will train the next generation of scientists who can tackle the challenges in the current food allergy assessment of novel food products.
ALLPreT will train early stage researchers (ESRs) in the core aspects of food allergy risk assessment, immunology, protein chemistry, bioinformatics, in vitro/in vivo/in silico model development and complementary “soft” skills to deliver well educated young scientists, with a unique position within the EU labour market.
ALLPreT will explore the new field of research on de novo sensitisation by novel foods and develop a toolbox with in vitro/in vivo/in silico allergenicity prediction tools that are scientifically sound, validated and easily usable by industry and food safety authorities. This toolbox will contribute to fast and accurate safety assessment, thereby speeding up safety approval and market uptake of novel foods.
Imptox
Plastic particles have been ubiquitously detected in the environments. Estimates suggest 5.25 trillion plastic particles currently circulate in ocean surface waters and a dramatic increase in plastic use and plastic waste has peaked also because of the COVID-19. Plastic polymers can be slowly degraded by microorganisms, heat, oxidation, light, or hydrolysis and result in the formation of micro and nano plastics (MNPs). The human body is constantly exposed to MNPs via skin, inhalation, and ingestion. Unfortunately, evaluation of the health impacts of environmental MNPs is hampered by a lack of information regarding chronic exposure levels, as well as how (micro)environmental weathering impacts MNP toxicity. Apart from their physical presence as environmental pollutants, concerns have been raised regarding some of the nonpolymeric components of MNPs. MNPs can act as vectors for the delivery of heavy metals, pathogenic microorganisms, proteins, and environmental and food contaminants into the body. There is a substantial lack of knowledge on binding of allergens to MNPs and their influence on the development of allergy. The overall concept underpinning the project is the evaluation of whether environmental or dietary exposure to MNPs augments allergenicity and can therefore impact human health, especially in sensitive populations with underlying health conditions. We plan to investigate, 1) the fate of MNPs in the gastrointestinal or respiratory tracts and secondary organs, and 2) the adjuvant potential of pure and contaminated particles during the induction of allergic asthma and food allergy.
Susinchain
As a partner of the Susinchain project, we will test for potential allergenicity to improve allergenicity risk assessment strategy required by industry and food safety authorities when assessing novel protein sources being introduced to the European consumers and ensure that the products adhere to relevant policies at the EU level for novel proteins including regulations. To test for potential allergenicity, we will assess whole unprocessed insects, processed components and frass determined by extracting the proteins and performing immunological characterisation IgE binding assays, Immunoblot in addition to determining cross-reactivity of the proteins from four species with known allergens such as tropomyosins from other sources like shrimp.
Th2 Memory
Individuals who are susceptible to allergic disease or are atopic may react to certain inhaled allergens like pollen or house dust mite by developing allergic asthma, which is a chronic inflammatory disease affecting the airways and is characterized by immune responses resulting in reversible airway obstruction and potential structural lung damage . Both in humans and in experimental animals, CD4+ T-helper (Th) lymphocytes central to the pathogenesis of allergic asthma have been extensively studied and, yet, the underlying mechanisms of this relapsing-remitting disease remain incompletely understood. To further dissect the role of Th cells, we established an allergen-induced relapsing-remitting experimental mouse model that mimics seasonal or intermittent bronchial asthma brought on by allergen sensitization and repeated exposure to the sensitizing allergen. In this model, long-lived allergen-specific memory CD4+ Th2 cells are present within cellular infiltrates in the lungs for the lifetime of the mouse, which corroborates findings in asthmatic patients who have Th2 cells in sputum, bronchoalveolar lavage fluid (BAL), and lung biopsies both during and out of allergy season. These observations either suggest that these Th2 memory cells recirculate through or persist in the lungs of patients and mice.
In mice recovered from their first episode of allergen-induced experimental asthma, there are quiescent Th2 memory cells within infiltrates near small, medium, and large airways. These T cells respond to inhaled allergen and then lead to disease relapse that mimics a seasonal human asthma attack with eosinophilic airway inflammation, mucus hypersecretion, and airway hyperresponsiveness (AHR). Although these long-lived lung Th2 memory cells are considered pathogenic, they have not been fully characterized. In recent years, tissue resident memory cells (TRMs) have been found in a variety of peripheral tissues including lungs and can be distinguished from circulating memory cells.
Mice with allergic asthma have allergen-specific Th2-TRMs residing in the lungs and acting as sentinels responding to allergen exposure and driving allergen-induced exacerbations of asthma, which is probably similar in asthmatic patients. In this project, we are attempting to understand the importance of TRMs in allergic asthma using a mouse model of relapsing-remitting experimental allergic asthma.
Ragweed
Ambrosia artemisiifolia, commonly known as ragweed, is an invasive North American plant. Ragweed pollen are allergenic and cause symptoms in sensitized atopic individuals. Sensitization to ragweed is predicted to more than double in Europe by 2060. Changes in the environment alter the pollen and could increase prevalence and disease severity. In this project, we are investigating potential differences in disease severity secondary to ragweed pollen from different origins in novel mouse models of pollen-induced asthma that closely resemble human disease.
Food allergy and GMOs
Food safety regulators request prediction of allergenicity for newly expressed proteins in genetically modified (GM) crops and in novel foods. Some have suggested using animal models to assess potential allergenicity. A variety of animal models have been used in research to evaluate sensitisation or elicitation of allergic responses. However, protocols for sensitisation and challenge, animal species and strains, diets and other environmental factors differ widely. In this project, we are seeking to develop novel experimental models of food allergy to evaluate the allergenicity of genetically modified organisms (GMOs) and novel foods.
Biomaterials and tissue regeneration
A promising approach in tissue repair, healing, and regeneration is the use of biomaterials created with bioactive components that amplify physiological mechanisms. However, a key feature of healing is the generation of an optimal milieu in which there is sufficient inflammatory signals initiating the response, but too much and/or chronic inflammation may delay and reduce tissue repair. Moreover, an allergic immune reaction to a biomaterial may generate inflammation that may also be detrimental to engraftment and repair. Therefore, for a biomaterial to enhance healing, it requires the capacity to generate inflammatory signals for healing without being immunogenic or allergenic. Inflammatory, immune, and fibrotic responses to foreign materials. The aim of this project is to use existing in vitro and in vivo approaches to assess inflammation, immune, allergic, and fibrotic responses secondary to biomaterials created for healing and tissue regeneration.
Genetics and Epigenetics
Understanding the development and chronic nature of allergic disease is crucial for finding new therapeutic approaches. We are using new analytics to define and identify genes and epigenetic marks expressed during the ongoing disease.