Helminth-derived glycoproteins and insulin sensitivity: from immunomodulatory properties to direct regulation of metabolic tissues
Projectomschrijving
In Nederland lijden meer dan een miljoen mensen aan type-2 diabetes en dat aantal groeit nog steeds. Het is bekend dat ontstekingen in bepaalde weefsels en organen leiden tot insulineresistentie met type-2 diabetes als gevolg, en het is dus belangrijk dat therapieën worden ontwikkeld die dit tegengaan. Onderzoekers van het LUMC gaan nieuwe behandelmethoden ontwikkelen op basis van hun kennis over parasitaire wormen. Tijdens een infectie beïnvloeden deze wormen het immuunsysteem en het metabolisme van hun gastheer en daarmee onderdrukken ze type-2 diabetes. De onderzoekers hebben bepaalde stoffen gevonden die de parasiet daarvoor gebruikt en wetenschappers van de WUR hebben een unieke manier ontwikkeld om deze stoffen na te maken in planten. Dit TOP consortium wil die stoffen nu gaan gebruiken om het metabolisme mee te reguleren, direct en via het immuunsysteem, met als uiteindelijk doel de insulinegevoeligheid bij mensen met type-2 diabetes te verhogen en zo de ziekte te bestrijden.
Producten
Titel: Chronic helminth infection and helminth-derived egg antigens promote adipose tissue M2 macrophages and improve insulin sensitivity in obese mice
Auteur: Hussaarts, Leonie, García-Tardón, Noemí, van Beek, Lianne, Heemskerk, Mattijs M., Haeberlein, Simone, van der Zon, Gerard C., Ozir-Fazalalikhan, Arifa, Berbée, Jimmy F. P., Willems van Dijk, Ko, van Harmelen, Vanessa, Yazdanbakhsh, Maria, Guigas, Bruno
Magazine: The FASEB Journal
Auteur: Hussaarts, Leonie, García-Tardón, Noemí, van Beek, Lianne, Heemskerk, Mattijs M., Haeberlein, Simone, van der Zon, Gerard C., Ozir-Fazalalikhan, Arifa, Berbée, Jimmy F. P., Willems van Dijk, Ko, van Harmelen, Vanessa, Yazdanbakhsh, Maria, Guigas, Bruno
Magazine: The FASEB Journal
Titel: The helminth glycoprotein omega-1 improves metabolic homeostasis in obese mice through
type-2 immunity-independent inhibition of food intake
Auteur: Hendrik J.P. van der Zande, Michael A. Gonzalez, Karin de Ruiter, Ruud H.P. Wilbers, Noemi Garcia-Tardón, Mariska van Huizen, Kim van Noort, Leonard R. Pelgrom, Joost M. Lambooij, Anna Zawistowska-Deniziak, Frank Otto, Arifa Ozir-Fazalalikhan, Danny van Willigen, Mick Welling, Jordan Poles, Fijs van Leeuwen, Cornelis H. Hokke, Arjen Schots, Maria Yazdanbakhsh, P’ng Loke, Bruno Guigas
Magazine: BioRxiv
Auteur: Hendrik J.P. van der Zande, Michael A. Gonzalez, Karin de Ruiter, Ruud H.P. Wilbers, Noemi Garcia-Tardón, Mariska van Huizen, Kim van Noort, Leonard R. Pelgrom, Joost M. Lambooij, Anna Zawistowska-Deniziak, Frank Otto, Arifa Ozir-Fazalalikhan, Danny van Willigen, Mick Welling, Jordan Poles, Fijs van Leeuwen, Cornelis H. Hokke, Arjen Schots, Maria Yazdanbakhsh, P’ng Loke, Bruno Guigas
Magazine: BioRxiv
Titel: Soluble mannose receptor induces pro-inflammatory macrophage activation and metaflammation
Auteur: Maria Embgenbroich, Hendrik J.P. van der Zande, Leonie Hussaarts, Jonas Schulte-Schrepping, Leonard R. Pelgrom, Noemí García-Tardón, Laura Schlautmann, Isabel Stoetzel, Kristian Händler, Joost M. Lambooij, Anna Zawistowska-Deniziak, Lisa Hoving, Karin de Ruiter, Marjolein Wijngaarden, Hanno Pijl, Ko Willems van Dijk, Bart Everts, Vanessa van Harmelen, Maria Yazdanbakhsh, Joachim L. Schultze, Bruno Guigas, Sven Burgdorf
Magazine: BioRxiv
Auteur: Maria Embgenbroich, Hendrik J.P. van der Zande, Leonie Hussaarts, Jonas Schulte-Schrepping, Leonard R. Pelgrom, Noemí García-Tardón, Laura Schlautmann, Isabel Stoetzel, Kristian Händler, Joost M. Lambooij, Anna Zawistowska-Deniziak, Lisa Hoving, Karin de Ruiter, Marjolein Wijngaarden, Hanno Pijl, Ko Willems van Dijk, Bart Everts, Vanessa van Harmelen, Maria Yazdanbakhsh, Joachim L. Schultze, Bruno Guigas, Sven Burgdorf
Magazine: BioRxiv
Titel: A worm of one's own: how helminths modulate host adipose tissue function and metabolism
Auteur: Guigas, Bruno, Molofsky, Ari B.
Magazine: Trends in Parasitology
Auteur: Guigas, Bruno, Molofsky, Ari B.
Magazine: Trends in Parasitology
Titel: Functional characterization of Schistosoma mansoni fucosyltransferases in Nicotiana benthamiana plants
Auteur: Kim van Noort, Dieu-Linh Nguyen, Verena Kriechbaumer, Chris Hawes, Cornelis H. Hokke, Arjen Schots & Ruud H. P. Wilbers
Magazine: Scientific Reports
Auteur: Kim van Noort, Dieu-Linh Nguyen, Verena Kriechbaumer, Chris Hawes, Cornelis H. Hokke, Arjen Schots & Ruud H. P. Wilbers
Magazine: Scientific Reports
Titel: Nicotiana benthamiana a-galactosidase A1.1 can functionally complement human a-galactosidase A deficiency associated with Fabry disease
Auteur: Kassiani Kytidou, Jules Beekwilder, Marta Artola, Eline van Meel, Ruud H. P. Wilbers, Geri F. Moolenaar, Nora Goosen, Maria J. Ferraz, Rebecca Katzy, Patrick Voskamp, Bogdan I. Florea, Cornelis H. Hokke, Herman S. Overkleeft, Arjen Schots, Dirk Bosch, Navraj Pannu and Johannes M. F. G. Aerts
Magazine: Journal of Biological Chemistry
Auteur: Kassiani Kytidou, Jules Beekwilder, Marta Artola, Eline van Meel, Ruud H. P. Wilbers, Geri F. Moolenaar, Nora Goosen, Maria J. Ferraz, Rebecca Katzy, Patrick Voskamp, Bogdan I. Florea, Cornelis H. Hokke, Herman S. Overkleeft, Arjen Schots, Dirk Bosch, Navraj Pannu and Johannes M. F. G. Aerts
Magazine: Journal of Biological Chemistry
Titel: De comeback van tabak als medicijn
Auteur: Peter de Jaeger
Magazine: Het Parool
Auteur: Peter de Jaeger
Magazine: Het Parool
Titel: Production and glyco-engineering of immunomodulatory helminth glycoproteins in plants
Auteur: Wilbers, Ruud H. P., Westerhof, Lotte B., van Noort, Kim, Obieglo, Katja, Driessen, Nicole N., Everts, Bart, Gringhuis, Sonja I., Schramm, Gabriele, Goverse, Aska, Smant, Geert, Bakker, Jaap, Smits, Hermelijn H., Yazdanbakhsh, Maria, Schots, Arjen, Hokke, Cornelis H.
Magazine: Scientific Reports
Auteur: Wilbers, Ruud H. P., Westerhof, Lotte B., van Noort, Kim, Obieglo, Katja, Driessen, Nicole N., Everts, Bart, Gringhuis, Sonja I., Schramm, Gabriele, Goverse, Aska, Smant, Geert, Bakker, Jaap, Smits, Hermelijn H., Yazdanbakhsh, Maria, Schots, Arjen, Hokke, Cornelis H.
Magazine: Scientific Reports
Titel: Helminths improve insulin sensitivity and enhance M2 macrophage numbers in WAT of obese mice
Auteur: Geach, T.
Magazine: Nature Reviews Endocrinology
Auteur: Geach, T.
Magazine: Nature Reviews Endocrinology
Titel: Schistosome egg antigens, including the glycoprotein IPSE/alpha-1, trigger the development of regulatory B cells
Auteur: Haeberlein, Simone, Obieglo, Katja, Ozir-Fazalalikhan, Arifa, Chayé, Mathilde A. M., Veninga, Henrike, van der Vlugt, Luciën E. P. M., Voskamp, Astrid, Boon, Louis, den Haan, Joke M. M., Westerhof, Lotte B., Wilbers, Ruud H. P., Schots, Arjen, Schramm, Gabriele, Hokke, Cornelis H., Smits, Hermelijn H.
Magazine: PLoS Pathogens
Auteur: Haeberlein, Simone, Obieglo, Katja, Ozir-Fazalalikhan, Arifa, Chayé, Mathilde A. M., Veninga, Henrike, van der Vlugt, Luciën E. P. M., Voskamp, Astrid, Boon, Louis, den Haan, Joke M. M., Westerhof, Lotte B., Wilbers, Ruud H. P., Schots, Arjen, Schramm, Gabriele, Hokke, Cornelis H., Smits, Hermelijn H.
Magazine: PLoS Pathogens
Titel: Snoep verstandig, eet een worm
Auteur: Braun, Bart
Magazine: Mare
Auteur: Braun, Bart
Magazine: Mare
Titel: Wormen kunnen diabetes type 2 voorkomen
Auteur: Roefs, Maaike
Magazine: DIABC
Auteur: Roefs, Maaike
Magazine: DIABC
Titel: Immune Regulation of Metabolic Homeostasis by Helminths and Their Molecules
Auteur: Hendrik J.P. van der Zande, Anna Zawistowska-Deniziak and Bruno Guigas
Magazine: Trends in Parasitology
Link: https://www.sciencedirect.com/science/article/pii/S1471492219301953?via%3Dihub
Auteur: Hendrik J.P. van der Zande, Anna Zawistowska-Deniziak and Bruno Guigas
Magazine: Trends in Parasitology
Link: https://www.sciencedirect.com/science/article/pii/S1471492219301953?via%3Dihub
Titel: Schistosoma haematobium infection is
associated with lower serum cholesterol
levels and improved lipid profile in
overweight/obese individuals
Auteur: Jeannot F. Zinsou, Jacqueline J. Janse, Yabo Y. Honpkehedji, Jean Claude Dejon-Agobe, Noemi Garcia-Tardon, Pytsje T. Hoekstra, Marguerite Massinga-Loembe, Paul L. A. M. Corstjens, Govert J. van Dam, Martin Giera, Peter G. Kremsner, Maria Yazdanbakhsh, Ayola A. Adegnika, Bruno Guigas
Magazine: PLoS Neglected Tropical Diseases
Auteur: Jeannot F. Zinsou, Jacqueline J. Janse, Yabo Y. Honpkehedji, Jean Claude Dejon-Agobe, Noemi Garcia-Tardon, Pytsje T. Hoekstra, Marguerite Massinga-Loembe, Paul L. A. M. Corstjens, Govert J. van Dam, Martin Giera, Peter G. Kremsner, Maria Yazdanbakhsh, Ayola A. Adegnika, Bruno Guigas
Magazine: PLoS Neglected Tropical Diseases
Titel: Editorial - Parasites and metabolic diseases
Auteur: Guigas, B.
Magazine: Parasite Immunology
Auteur: Guigas, B.
Magazine: Parasite Immunology
Titel: Stoffen uit wormeneitjes goed voor metabolisme
Auteur: LUMC communication department
Magazine: LUMC Nieuwsbrief
Auteur: LUMC communication department
Magazine: LUMC Nieuwsbrief
Titel: The Schistosoma mansoni glycoprotein omega-1 improves whole-body metabolic homeostasis independent of its Th2 polarizing capacity
Auteur: HENDRIK VAN DER ZANDE
Auteur: HENDRIK VAN DER ZANDE
Titel: Immune-dependent and -independent regulation of metabolic homeostasis by helminth molecules
Auteur: Guigas, Bruno
Auteur: Guigas, Bruno
Titel: Helminth antigens improve insulin sensitivity in obese mice by promoting a STAT6-dependent type 2 immune response in white adipose tissue
Auteur: van der Zande, Patrick
Auteur: van der Zande, Patrick
Titel: Immune regulation of metabolic homeostasis by helminths
Auteur: Guigas, Bruno
Auteur: Guigas, Bruno
Titel: Using plants to characterise Schistosoma mansoni fucosyltransferases
Auteur: van Noort, Kim
Auteur: van Noort, Kim
Titel: Helminth antigens improve insulin sensitivity in obese mice by promoting a STAT6-dependent type 2 immune response in white adipose tissue
Auteur: van der Zande, Patrick
Auteur: van der Zande, Patrick
Titel: Immune regulation of metabolic homeostasis by parasite molecules
Auteur: Bruno Guigas
Auteur: Bruno Guigas
Titel: The Schistosoma mansoni glycoprotein omega-1 improves whole-body metabolic homeostasis independent of its Th2 polarizing capacity
Auteur: Hendrik van der Zande, Michael Gonzalez, Mariska van Huizen, Karin de Ruiter, Ruud Wilbers, Lotte Westerhof, Arjen Schots, P’ng Loke, Maria Yazdanbakhsh, Bruno Guigas
Auteur: Hendrik van der Zande, Michael Gonzalez, Mariska van Huizen, Karin de Ruiter, Ruud Wilbers, Lotte Westerhof, Arjen Schots, P’ng Loke, Maria Yazdanbakhsh, Bruno Guigas
Titel: Phenotypically distinct alternatively-activated adipose tissue macrophages induced by helminth molecules differently impact metabolic homeostasis
Auteur: H. J. P. van der Zande
Auteur: H. J. P. van der Zande
Titel: Immune regulation of metabolic homeostasis by helminths
Auteur: Guigas, Bruno
Auteur: Guigas, Bruno
Titel: Immune regulation of metabolic homeostasis by helminth molecules
Auteur: Guigas, Bruno
Auteur: Guigas, Bruno
Titel: "One triple shot americano and a coconut-chocolate-oats bar, please"; de effecten van parasitaire wormen op de stofwisseling
Auteur: van der Zande, Patrick
Auteur: van der Zande, Patrick
Titel: The Schistosoma mansoni glycoprotein omega-1 improves whole-body metabolic homeostasis independent of its Th2 polarizing capacity
Auteur: van der Zande, Patrick
Auteur: van der Zande, Patrick
Titel: Characterization of Schistosoma mansoni fucosyltransferases for glyco-engineering of ‘native’ helminth N-glycan structures in planta
Auteur: Van Noort, Kim Wilbers, Ruud H.P. Westerhof, Lotte B. Smant, G Bakker, J Schots, Arjen
Auteur: Van Noort, Kim Wilbers, Ruud H.P. Westerhof, Lotte B. Smant, G Bakker, J Schots, Arjen
Titel: Helminth antigens improve glucose tolerance in obese mice by promoting a STAT6-dependent type 2 immune response in white adipose tissue
Auteur: van der Zande Hendrik J.P. Gonzalez Michael Gundra, Uma M. Lin Jian-Da Hokke, Cornelis H. Yazdanbakhsh, Maria Loke, P’ng Guigas, Bruno
Auteur: van der Zande Hendrik J.P. Gonzalez Michael Gundra, Uma M. Lin Jian-Da Hokke, Cornelis H. Yazdanbakhsh, Maria Loke, P’ng Guigas, Bruno
Titel: Characterization of Schistosoma mansoni fucosyltransferases for glyco-engineering of ‘native’ helminth N-glycan structures in planta
Auteur: Van Noort, Kim Wilbers, Ruud H.P. Westerhof, Lotte B. Smant, G. Bakker, J. Schots, Arjen
Auteur: Van Noort, Kim Wilbers, Ruud H.P. Westerhof, Lotte B. Smant, G. Bakker, J. Schots, Arjen
Titel: Chronic treatment with helminth-derived egg antigens improves whole-body metabolic homeostasis and insulin sensitivity in obese mice
Auteur: Garcia-Tardon, Noemi
Auteur: Garcia-Tardon, Noemi
Titel: Phenotypically distinct alternatively-activated adipose tissue macrophages induced by helminth molecules differently impact metabolic homeostasis
Auteur: Hendrik J. P. van der Zande
Auteur: Hendrik J. P. van der Zande
Titel: Helminth infection and metabolic syndrome
Auteur: Guigas, Bruno
Auteur: Guigas, Bruno
Titel: The helminth glycoprotein omega-1 improves whole-body metabolic homeostasis independent of its Th2 polarizing capacity
Auteur: Hendrik van der Zande, Michael Gonzalez, Mariska van Huizen, Karin de Ruiter, Ruud Wilbers, Lotte Westerhof, Arjen Schots, P’ng Loke, Maria Yazdanbakhsh, Bruno Guigas
Auteur: Hendrik van der Zande, Michael Gonzalez, Mariska van Huizen, Karin de Ruiter, Ruud Wilbers, Lotte Westerhof, Arjen Schots, P’ng Loke, Maria Yazdanbakhsh, Bruno Guigas
Titel: Immune regulation of metabolic homeostasis by helminths and their molecules
Auteur: Bruno Guigas
Auteur: Bruno Guigas
Titel: Engineering of plants for the expression of helminth glycoproteins with their native N-glycan structures
Auteur: Wilbers, Ruud H.P. Westerhof, Lotte B. van Noort, Kim Nguyen, D-L. Bakker, J. Hokke, Cornelis H. Schots, Arjen
Auteur: Wilbers, Ruud H.P. Westerhof, Lotte B. van Noort, Kim Nguyen, D-L. Bakker, J. Hokke, Cornelis H. Schots, Arjen
Titel: Immune regulation of metabolic homeostasis by helminths and their molecules
Auteur: Bruno Guigas
Auteur: Bruno Guigas
Titel: Helminth antigens improve insulin sensitivity in obese mice by promoting a STAT6-dependent type 2 immune response in white adipose tissue
Auteur: van der Zande, Patrick
Auteur: van der Zande, Patrick
Titel: Characterization of Schistosoma mansoni fucosyltransferases for glyco-engineering of ‘native’ helminth N-glycan structures in planta
Auteur: van Noort, Kim Wilbers, Ruud H.P. ter Horst, Kasper Westerhof, Lotte B. Hokke, Cornelis H. Smant, G. Bakker, J Schots, Arjen
Auteur: van Noort, Kim Wilbers, Ruud H.P. ter Horst, Kasper Westerhof, Lotte B. Hokke, Cornelis H. Smant, G. Bakker, J Schots, Arjen
Titel: Phenotypically distinct alternatively-activated adipose tissue macrophages induced by helminth molecules differently impact metabolic homeostasis
Auteur: Bruno Guigas
Auteur: Bruno Guigas
Titel: Characterization of Schistosoma mansoni fucosyltransferases for glyco-engineering of
‘native’ helminth N-glycan structures in planta
Auteur: van Noort, Kim
Auteur: van Noort, Kim
Titel: Engineering of plants for the expression of helminth glycoproteins with their native N-glycan structures
Auteur: Wilbers, Ruud H.P. Westerhof, Lotte B. Everts, Bart van Noort, Kim van Raaij, Debbie R. Nguyen, Dieu-Linh Yazdanbakhsh, Maria Hokke, Cornelis H. Schots, Arjen
Auteur: Wilbers, Ruud H.P. Westerhof, Lotte B. Everts, Bart van Noort, Kim van Raaij, Debbie R. Nguyen, Dieu-Linh Yazdanbakhsh, Maria Hokke, Cornelis H. Schots, Arjen
Titel: Direct regulation of hepatic gluconeogenesis by helminth-derived molecules
Auteur: Guigas, Bruno
Auteur: Guigas, Bruno
Titel: Characterization of Schistosoma mansoni fucosyltransferases for glyco-engineering of
‘native’ helminth N-glycan structures in planta
Auteur: van Noort, Kim
Auteur: van Noort, Kim
Titel: Engineering of plants for the expression of helminth glycoproteins with their native N-glycan structures
Auteur: Wilbers, Ruud H.P. Westerhof, Lotte B. Everts, Bart van Noort, Kim van Raaij, Debbie R. Nguyen, Dieu-Linh Yazdanbakhsh, Maria Hokke, Cornelis H. Schots, Arjen
Auteur: Wilbers, Ruud H.P. Westerhof, Lotte B. Everts, Bart van Noort, Kim van Raaij, Debbie R. Nguyen, Dieu-Linh Yazdanbakhsh, Maria Hokke, Cornelis H. Schots, Arjen
Titel: Immune regulation of metabolic homeostasis by helminths and their molecules
Auteur: Bruno Guigas
Auteur: Bruno Guigas
Titel: Protective effects of parasite-derived molecules on metabolic disorders
Auteur: Guigas, Bruno
Auteur: Guigas, Bruno
Titel: Immune regulation of metabolic homeostasis:
from general concepts to therapeutic modulation by helminths
Auteur: Guigas, Bruno
Auteur: Guigas, Bruno
Titel: Immune regulation of metabolic homeostasis by helminths and their molecules
Auteur: Bruno Guigas
Auteur: Bruno Guigas
Titel: Interview in De Ochtendspits (BNR Nieuwsradio)
Auteur: Schots, Arjen
Auteur: Schots, Arjen
Titel: Immunomodulatory effects of parasites and metabolic syndrome
Auteur: Guigas, Bruno
Auteur: Guigas, Bruno
Titel: Immune regulation of metabolic homeostasis by helminths and their molecules
Auteur: Bruno Guigas
Auteur: Bruno Guigas
Titel: Immune regulation of metabolic homeostasis
Auteur: Bruno Guigas
Auteur: Bruno Guigas
Titel: Determination of Adenine Nucleotide Concentrations in Cells and Tissues by High-Performance Liquid Chromatography
Auteur: Noemí García-Tardón, Bruno Guigas
Auteur: Noemí García-Tardón, Bruno Guigas
Titel: Assessing Mitochondrial Bioenergetics by Respirometry in Cells or Isolated Organelles
Auteur: Guillaume Vial, Bruno Guigas
Auteur: Guillaume Vial, Bruno Guigas
Titel: HelP-T2D / Helminth products for Type 2 Diabetes
Auteur: Bruno Guigas Jantien Guldemond-Nieuwland
Link: http://help-t2d.nl/
Auteur: Bruno Guigas Jantien Guldemond-Nieuwland
Link: http://help-t2d.nl/
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Samenvatting van de aanvraag
Insulin resistance and type 2 diabetes are rising at an alarming rate affecting 382 million people worldwide and expected to rise to 592 million by 2035. Although pharmacological treatments are currently available for T2D and metabolic disorders, new innovative strategies are still needed for providing alternatives to progressive drug resistance to conventional medicines. Recent landmark studies have shown that type-2 immune responses are associated with improved insulin sensitivity and glucose homeostasis. This is supported by the ability of helminthes, the strongest natural stimuli of Type-2 responses, to improve whole-body glucose metabolism and insulin sensitivity in models of insulin resistance. Over the past year, it has been shown that helminth-extracts, can also improve insulin sensitivity, which indicates that the beneficial effects of helminths is via their modulatory effects rather than “parasitism” on caloric intake.
We have reported the identification of omega-1, an immunomodulatory glycoprotein released from Schistosoma mansoni helminth eggs, which drives Th2 responses . By dissecting the underlying mechanisms, we have demonstrated that glycan structure and enzymatic activity of omega-1 are both needed for inducing Th2 polarization. Further analysis and modification of its N-glycan structures showed that fucosylated antennae (LeX, LDN-F) mediate the omega-1-induced Th2 responses. Interestingly, soluble egg antigens and a structurally related synthetic polyvalent LeX glycoconjugate, were recently shown to improve glucose tolerance and insulin sensitivity in obese mice not only by immune-dependent mechanisms but also by directly modulating lipid metabolism in hepatocytes. Taken together,these data indicate that glycosylated proteins from helminthes (Helminth-Glycoproteins) might constitute a source of unique molecules for manipulating metabolic processes, either by triggering tissue-specific Th2 immune responses and/or by directly targeting metabolic cells via glycan-mediated interaction with specific receptors.
The recent development of pioneering technology in plants is opening new avenues for large scale recombinant glycoprotein production while allowing controlled modifications to create defined glycoforms by engineering the glycosylation machinery of the plant. This provides unprecedented opportunities to obtain large quantities of biologically active glycoproteins that can be manipulated structurally to study in detail the interaction with immune cells as well as organs that contribute to metabolic homeostasis.
The current proposal constitutes a collaborative interdisciplinary project which will characterize type-2 immune responses induced by Helminth-Glycoproteins that influence whole-body glucose/lipid metabolism and insulin sensitivity. Moreover, and importantly, it will assess the immune-independent direct effects of Helminth-Glycoproteins on adipose tissue and the liver, two of the important organs that control glucose/lipid metabolism, Complementary in vivo and in vitro approaches will be used to understand the mechanisms behind the metabolic actions of Helminth-Glycoproteins. Glycoengineering strategies in plants will provide endotoxin-free wild-type and mutant glycoproteins, to unravel the structural requirements and receptors involved in the protection against insulin resistance.
Within the consortium, the strong link to the human studies both in terms of the immune system, access to primary cells such as adipocytes and hepatocytes, as well as parallel clinical studies on metabolic disorders in areas where helminth infections are endemic is expected to facilitate translation of the fundamental knowledge into the human context. Through the link with industrial partners, and through Technology Transfer Offices of our academic centers, we realistically expect to move towards product development. Plants are a relatively new production host for biopharmaceutical proteins. However, the recent approval of plant-produced glucocerebrosidase (a glycoprotein) to treat the lysosomal storage disorders shows the potential of this production platform.
Taken together, this project at the interface between immunology/glycobiology and metabolism is expected to provide new findings and to identify metabolically active glycoproteins and/or cellular targets that can ultimately lead to future therapeutic opportunities for the treatment of metabolic disorders in humans.