Tau solid transition in neurons: its effect on axonal transport and how to prevent it

Area of Knowledge: Human Biology, Microbiology, Molecular Biology, Genetics, Cellular Biology, Genomics and Proteomics, Biochemistry

External Clinician co-director:

José Antonio Del Río Fernández, Institute for Bioengineering of Catalonia (IBEC) ·
Neurotechnology group

External Clinician co-director:

Alberto LLeó, Sant Pau Memory Unit ·
Sant Pau Memory Unit


Alzheimer’s Disease (AD) affects around 50 million people worldwide and, despite tremendous effort to find a treatment, little success has been achieved. This highlights the need for a better understanding of the disease’s mechanisms. This project aims to tackle this need by investigating the early stages of neuronal degeneration in AD, at the axon and synapse level, using a live cell imaging approach. Due to their morphology, neurons are particularly susceptible to traffic jams. Tau, one of the key players in AD, is a microtubule associated protein found transiently interacting with microtubules in healthy axons. In AD, this protein transition into solid aggregates. However, how tau initial transition affects axonal transport is unknow, but it seems essential to understand its role in AD. First, we will use a seeding strategy to trigger tau solid transition in neurons derived from human iPSCs with endogenous tau meGFP-tagged. Second, we will study the immediate consequences of this transition for axonal transport. Third, we will screen for potential inhibitors of this initial transition. Finally, we will reproduce these experiments in animal models. Intravital microscopy, already available at IBEC, will be used for this. This project joints common efforts of our group at IBEC and the group of Dr. Alberto LLeó at the Sant Pau Hospital in Barcelona to approach our research to the clinical knowledge. The project will also benefit from the expertise on optical imaging and pharmacoptogenetics of Dr. Pau Gorostiza group at IBEC. Overall, we aim to find helpful insights into tau role in AD and how to prevent it.

Our team uses state of the art technology, cellular and animal models to understand different neurodegenerative diseases. We also explore new therapeutic avenues to treat these devastating diseases. To this end, we have generated lab on chips and organoids to best mimic the neuronal environment and improve the screen potential of our models.


The successful applicant will study tau solid transition and its immediate consequences for axonal transport in neurons using a live cell imaging approach. Further, she/he will screen among target candidates that could prevent this initial transition. We are looking for a motivated and curious student, ideally with a background on Cell Biology, Biochemistry or Biomedicine. We would like a person that likes to work both in a team and independently. During this time, he/she will acquire skills on general laboratory work and good scientific practices. She/he will receive training on protein purification and how to generate tau seeds from recombinant tau. In parallel, he/she will seed tau aggregation using human samples from the well characterized AD SPIN cohort, available at Dr. Alberto LLeó group. The PhD student will also acquire extensive experience to work with human iPSC and their differentiation into mature neurons (2D and 3D models). In addition, she/he will get hands on state of the art microscopes, fluorescent-based microscopy techniques and microfluidic devices. He/she will also learn to quantify and analyse data semi-automatically. Weekly individual meetings with the group leader, as well as regular presentations in group meetings will ensure appropriate supervision and development of both scientific and transferable skills. The student will get mentoring on writing research articles and how to present his/her data to a scientific audience. The collaborations with the clinician group (Sant Pau Hospital) as well as with other groups at IBEC or internationally will also take place on those parts of the project that requires additional expertise/tools. Networking will be promoted through these collaborations, as well as by attending scientific conferences. Overall, we aim that during this time the student will acquire the scientific and transferable skills necessary to successfully carry out research projects, achieve and communicate breakthrough discoveries.

Additional websites

This is the web site of the group of Dr. Pau Gorostiza, that will support the project and the student with his expertise in optogenetics and optical imaging.