Molecular and Cellular Neurobiotechnology

Our research interests are focused on three main aspects of developmental neurobiology and neurodegeneration: development of new lab on chip devices for neurobiological research, new strategies to avoid α-synuclein and tau transport in neurons and new approaches to enhance axon regeneration after lesion.

Development of new lab on chip devices for neurobiological research 

One of our focus is to mimic the developing and neurodegenerating nervous system in lab on chip devices. We believe that combining several different stimuli in the chip resembles a more realistic environment that nerve cells will encounter in the living animal in normal and disease conditions. These experiments using la bon chip models in turn will make future studies on the role of neuronal cells in development and regeneration more accurate and complete. Thus, we developed a new device able to reproduce the formation of the neuromuscular junction (NMJ) in lab on chip devices. In addition, a device designed to analyse axon lesions of cortical neurons was also developed.

We developed a new device able to reproduce the formation of the neuromuscular junction (NMJ) in lab on chip devices.

Current experiments of our group in collaboration with groups of IBEC, CIBER-BBN, and other labs aimed at developing new lab on chip devices to mimics and modulate particular neurobiological processes. For example: i) on chip lab platform to monitor drug delivery modulating neuronal activity (see figure); ii) cortico-spinal chips to develop axon regenerative studies of new drug formulation (in collaboration with Imperial College; London); iii) devices tmigrating neurons (in collaboration with i3A, Zaragoza) and, iv) in silico 3D modeling for neurodegenerative diseases (Alzheimer and Parkinson chip).

Last experiments are focused to reproduce a lab on chip devices to analyse and to reproduce ALS models (in collaboration(Alzheimer and Parkinson chip). Last experiments are focused to reproduce a lab on chip devices to analyse and to reproduce ALS models (in collaboration with Biodonostia Hospital) (Figure 2).

New strategies to avoid α-synuclein and tau transport in neurons 

α-Synuclein is a key player in the pathogenesis of synucleinopathies, including Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. Transmission of synthetic α-synuclein aggregates has been demonstrated in several cellular and animal models. Several groups have reported that insoluble α-synuclein shows “prion-like” propagation in wild-type mice. However, the basis of the spreading process remains poorly understood although cell to cell transport via exocytosis has been proposed. We described in 2018 that PrPC is a new receptor for α-synuclein involved in their spreading and propagation. Our new objectives aimed to block this interaction to reduce the neuropathological transport of α-synuclein. Similar experiments are also developed in the case of tau, one of the hallmarks of Alzheimer´s disease, since tau also binds to PrPC during its inter-neuronal propagation. 

New approaches to enhance axon regeneration after lesion 

 Following axonal lesions in the adult CNS, damaged axons degenerate, while surviving fibres are unable to regenerate, and have a limited capacity to sprout and to re-establish lost connections. Experimental evidence suggests that providing a permissive extracellular environment containing cellular or biomaterial bridges is not enough to increase axon regrow to obtain functional regeneration, supporting the importance of clarifying the complex transcriptional response below these signalling pathways. As an alternative, activating or recapitulating the developmental program of the lesioned neuron to sprout and regenerate may represent a complementary therapeutic approach and may sometimes directly counteract the inhibitory signalling. Optogenetics is currently the state-of-the-art method for activity-based nervous system research, allowing more specific cellular stimulations by light in a less invasive techniques compared to classical electrical stimulation, but leading to a more tailored physiological response3. In our laboratory, we started to analyse whether optical stimulation of lesioned neurons is able to enhance axonal growth or sprouting. These experiments were performed on lesioned cortical neurons in vitro and in vivo.  

José Antonio Del Río Fernández

Group Leader

+34 934 020 296

jadelrioibecbarcelona.eu

Researcher profile

• Jordi Duran Castells, associated researcher

• Neural stem cell culture
• Microscopy facility (Olympus BX61 and Olympus IX71 with LCi culture and OKOlab systems)
• Electroporation system (BTX 600)
• Pressure microinjection system
• Protein expression and purification systems
• Technology of neuronal culture facilities (2D and 3D)
• Lentiviral production and characterization
• Protein and DNA electrophoresis
• In situ hybridization oven
• Optogenetic in vitro and in vivo stimulation system

• Dr. Adolfo Lopéz de Munain
  Hospital de Donostia, San Sebastian, Spain
• Dr. Joaquin Castilla
  CiC Biogune, Bilbao, Spain
• Prof. Juan María Torres
  INIA-CISA CSIC, Valdeolmos, Madrid, Spain
• Prof. José María Delgado and Prof. Agnest Gruart,
  UPO, Sevilla, Spain
• Prof. Jose Manuel García Verdugo
  Facultad de Ciencias, Universidad de Valencia, Spain
• Prof. Jose Manuel García Aznar
  Nanotechnology Institute, Zaragoza, Spain
• Prof. Fernando Albericio and Ernest Giralt
  Institute for Research in Biomedicine (IRB), Barcelona
• Dr. Miriam Royo
  Institute for Research in Biomedicine (IRB), Barcelona
• Dr. Elisabeth Engel, Prof. Josep Samitier, Prof. Xavier Trepat and Prof. Daniel Navajas
  IBEC
• Prof. Ángel Raya
  Center of Regenerative Medicine in Barcelona (CMRB)
• Dr. Antonella Consiglio and Dr. Franc LLorens
  Institut d’Investigació Biomèdica de Bellvitge, University of Barcelona, Spain
• Prof. Jesús Ávila and Prof. Francisco Wandosell
  Consejo Superior de Investigaciones Científicas (CSIC), Universidad Autónoma de Madrid, Spain
• Prof. Isidro Ferrer
  Institut d’Investigació Biomèdica de Bellvitge, University of Barcelona, Spain
• Dr. Alberto LLeó
  Hospital Sant Pau, Barcelona, Spain
• Prof. Miquel Vila
  VHIR, Barcelona, Spain
• Prof. Fanny Mann
  Developmental Institute of Marseille Luminy, Université de la Méditerranée, Marseille, France
• Prof. Yutaka Yoshida
  Division of Developmental Biology, Cincinnati Children’s Research Foundation, Cincinnati, Ohio, USA
• Prof. Masato Hagesawa
  Faculty of Medicine, Tokyo
• Prof. José Luis Lanciego
  CIMA, Navarra, Spain