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Final Report Summary - GLYCOPAR (Parasite glycobiology and anti-parasitic strategies)

Human infections caused by parasitic protozoans and helminths are among the world-leading causes of death. Several million people die each year from diseases like malaria, leishmaniasis, trypanosomiasis and schistosomiasis and million more endure disabilities that cause lifelong suffering. Many of these parasites infect commercially valuable animals causing economic losses that are often not appreciated. Although less common in developed countries, these parasitic infections are present among immigrants and travellers returning from endemic regions and provide an increasing threat for immunocompromised individuals (e.g. AIDS patients). Furthermore, environmental and climate changes can affect the breeding, development and proliferation of specific parasite species and their vectors or hosts, increasing the risk of introduction (or re-introduction) of certain parasitic diseases in Europe. In addition, in western countries, other parasites such as Acanthamoeba sp. cause disease in immunocompromised individuals, while Trichomonas vaginalis is probably the most widespread sexually-transmitted infection worldwide.

Parasites usually present complex life cycles and need to exploit sequentially more than one host species involving different stages. Thus, parasites have evolved to deceive and compromise the immune systems of the different infected organisms with great success. Cell-cell interactions between the parasite and the different hosts are critical for the successful completion of each life stage and often these interactions are mediated by glycans, which are essential for parasite virulence. Furthermore, glycoconjugates on the surface of the parasite usually form a protective barrier against the host defence systems. Therefore, research into parasite glycobiology allows not only to tackle the aforementioned worldwide human health problems, but also to acquire important new insights into molecular pathology and host-pathogen interactions.

The principal objective of the parasite glycobiology and anti-parasitic strategies initial training network (GLYCOPAR) was the training of a new generation of scientists with the skills and knowledge demanded to address the challenges involved in the study of parasite glycobiology and the translation of this research into successful therapeutic strategies.

This Network combined the training of early stage researchers (ESR) in research and transferable skills with an ambitious program of training-through-research, implemented via 13 well-devised research projects covering different paramount topics on parasite glycobiology. The main scientific goal of GLYCOPAR was the description of novel paradigms and models by which parasite glycoconjugates play a role in the successful colonization of the different hosts. To this end, GLYCOPAR research was divided into four work-packages that aim to outline: 1) The structures of parasite glycans (the glycome), as well as the enzymes involved in their biosynthesis; 2) The properties of parasite glycans and their specificity and affinity for glycan-binding receptors in the host; 3) The fundamental function and the importance of these glycans in host-pathogen interactions and 4) The translation of all this knowledge into novel diagnostic tools and therapeutic approaches against parasitic infections affecting humans or animals.

To accomplish these ambitious aims GLYCOPAR involved 14 partner institutions, 8 academic laboratories and 6 industrial partners from 7 different nations across Europe. The work carried out by the recruited fellows involved 1) The develop of ABPP probes to identify novel glycosyltransferases, 2) the origin and role of D-arabinopyranose in kinetoplastids; 3) essentiality and role of sugar nucleotide metabolism in Plasmodium; 4) protein and substrate specificities of apicomplexa OST complex; 5) C-mannosylation in apicomplexa; 6) surface glycans in metacyclic stages of Trypanosoma brucei; 7) structural studies of nematode GalT-1; 8) development of a protective vaccine against dog’s heartworm; 9) structure based inhibitor design against Leishmania pyrophosphorylase; 10) the integration of glycomics data in large scale genomic data; 11) the essentiality and role of Plasmodium OST; 12) the description of amoebal glycoconjugates and 13) development of high-throughput analytical techniques to analyse parasite glycans.

To date several scientific results have been obtained and all the fellows presented their work in multiple international scientific meetings, congresses and seminars. In addition, an increasing number of publications have now been published and more will follow in the forthcoming months. Fifteen joint publications have materialized in the last four years. One publication in PLOS Pathogens depicting the objectives of the GLYCOPAR ITN and involving all the Network partners is worth a special mention.

The training programme developed as expected with: 1) a great focus on Training-through-research in intellectually exciting and state-of-the-art supportive environments; 2) inter-sectorial and transnational mobility via secondments and shorter visits between academic and industrial partners; 3) Local training in core research skills within both academic and industrial environments; 4) Network-wide training, in generic or specialised S&T aspects and complementary transferable and 5) Implementation of outreach activities by the recruited fellows.

Overall the GLYCOPAR ITN developed well and all the participating members contributed significantly to the body of knowledge regarding the diversity and pervasiveness of glycans in parasite biology through an integrated effort across many disciplines, with the use of state-of-the-art technologies and the collaborative efforts of world-class research institutions. This network provided a strong, multidisciplinary training for early-stage researchers on the biosynthetic, structural and functional characterisation of glycoconjugates of parasites responsible for life-threatening diseases. Some of the recruited fellows have now defended their PhD thesis and have easily progressed to work in top institutions in Europe and Asia, reinforcing the usefulness of the skills acquired in this ITN to the current job market.

More information about the activities developed by this ITN can be found in the GLYCOPAR project website, http://www.glycopar.eu and through social media pages, https://www.facebook.com/glycopar and http://www.twitter.com/glycopar

Reported by

INSTITUTO DE MEDICINA MOLECULAR
Portugal

Subjects

Life Sciences
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