Use of nano-bioconjugates as the next generation of imaging agents for Alzheimer's disease

Alzheimer’s disease is recognized worldwide as a public health priority due to its increase in prevalence with age, to near pandemic extent by 2050. However, there is currently only one FDA-approved disease-modifying treatment for Alzheimer’s disease. There is therefore an urgent need to improve the diagnosis of Alzheimer’s disease and related disorders, and to develop disease-modifying therapies.

This PhD position is part of the European MSCA TAME project (https://tame-itn.eu). The aim of this European consortium is to contribute to a better understanding of tau-related diseases and supports the development of new, safer, personalised and more effective diagnosis and interventions for Alzheimer’s disease (AD) and the less common tauopathies. 

The objective of the project in Liège is to develop a Nanobody-based PET imaging tracer for highly specific and sensitive detection and quantification of pathological Tau protein in the brain of Alzheimer’s diseases transgenic mice models. To reach this aim the project will involve the following tasks: (i) Select the anti-pathological Tau Nb (Nb-tauP) that diffuses the best into the brain parenchyma of AD mice and label NFTs following intra intracerebral injection. (ii) Fuse, by genetic engineering, this Nb to cell-penetrating peptides or to Nbs known to increase BBB-passage by transcytosis (anti-transferrin receptor-TfR). (iii) Produce and characterize in vitro the properties of the modified Nbs, (iii) Label the Nb-tauP and their modified versions with ¹⁸F. (iii) Investigate different routes of injection of ¹⁸F-Nbs on their ability to cross the BBB. (iv) Carry out in vivo ¹⁸F-PET imaging using the best Nb-tauP-based functionalised Nb and the best delivery route of Nb-Tau in ThyTau22 mice model.

The candidate will obtain the PhD degree from the University of Liège. The candidate will be working under the joint supervision of P. Maquet, T. Gendron and M. Dumoulin at both GIGA-In Vivo Imaging (https://www.gigacrc.uliege.be/cms/c_4212477/fr/gigacrc) and the Center for Protein Engineering (http://labos.ulg.ac.be/cip/), which are very close by. Both Centers are highly multidisciplinary and opened to collaborations. The daily activities of the PhD candidate consist mainly in research but it is also expected that the candidate participates to the TAME training activities. The candidate has the possibility to develop collaborations with other members of the TAME consortium and to visit their laboratory in order to broaden his fields of expertise. In particular, two 3-month secondments are scheduled during the PhD, in laboratories of TAME partners: 1^st secondment at the Biomedical Sciences Research Center “Alexander Fleming” – Institute for Fundamental Biomedical Research (Vari, Greece) supervised by E. MC SKOULAKIS & K. PAPANIKOLOPOULOU, in order to use mouse model to assay brain delivery. 2^nd secondment at DeepLife (Paris, France) supervised by J. MORLOT to cross-validate intraneuronal tau markers with digital models.

Candidates must have a Master in Biomedical Sciences, Biochemistry or related disciplines; a strong knowledge in protein biochemistry is required, knowledge in radiochemistry and experience with mice experiments is highly beneficial but not mandatory. Candidates should be highly motivated and creative; they should have an ability to work independently and as part of a multidisciplinary team. Moreover, they should have an excellent organization, communication and team skill. Candidates must possess a European Master’s degree or equivalent at the application deadline. The candidate must have an excellent proficiency of English (based on the TOEFL test).The candidate must not have resided or carried out their main activity (work, studies, etc.) in Belgium for more than 12 months in the 3 years immediately prior to the start of the contract date