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A Personalised Living Cell Synthetic Computing Circuit for Sensing and Treating Neurodegenerative Disorders

Objective

There remain urgent and unmet needs for the treatment of neurological diseases. Epilepsy is a serious, chronic brain disease characterized by recurrent seizures. Closed-loop, implanted devices offer ways to reduce seizures in drug-resistant patients but their efficacy is poor and they interrupt seizures only after they begin. PRIME capitalizes on a breakthrough discovery that transfer RNA (tRNA) fragments, a novel class of noncoding RNA, increase in patients in advance of when a seizure occurs. We propose to engineer human cells to respond to tRNA fragment elevations as the trigger for pre-emptive release of glial-derived neurotrophic factor (GDNF), a seizure-suppressing and disease-modifying treatment. Artificial Intelligence (AI) algorithms will be used to integrate OR or AND logic gate functions in the switching process, depending on the quantity and type of tRNA fragments and timing of their release in a given epileptic network and a second, fail-safe calcium-dependent pathway will allow GDNF release in the event of a breakthrough seizure. This enables a precise level of personalization in the design of the bio-computing cells, which will be encapsulated into a membrane device within the microenvironment scaffold, enabling the engineered cells to co-exist with natural brain tissue. Validation of the bio-computing cells will be tested in both in vitro microfluidic organ-on-a-chip as well as in vivo tests for effects on spontaneous seizures in rodents with epilepsy. PRIME’s results will provide a transformational diagnostic-therapeutic treatment for epilepsy and other neurological diseases that feature disrupted neuronal network function.

Field of science

  • /engineering and technology/other engineering and technologies/microtechnology/organ on a chip
  • /natural sciences/biological sciences/genetics and heredity/rna
  • /natural sciences/computer and information sciences/artificial intelligence
  • /medical and health sciences/basic medicine/neurology/epilepsy

Call for proposal

H2020-FETOPEN-2018-2019-2020-01
See other projects for this call

Funding Scheme

RIA - Research and Innovation action

Coordinator

WATERFORD INSTITUTE OF TECHNOLOGY
Address
Cork Road
X91 Waterford
Ireland
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 706 875

Participants (6)

AARHUS UNIVERSITET
Denmark
EU contribution
€ 641 940
Address
Nordre Ringgade 1
8000 Aarhus C
Activity type
Higher or Secondary Education Establishments
Omiics ApS
Denmark
EU contribution
€ 476 875
Address
Åbogade 15
8200 Aarhus N
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
ROYAL COLLEGE OF SURGEONS IN IRELAND
Ireland
EU contribution
€ 781 835
Address
Saint Stephen's Green 123
2 Dublin
Activity type
Higher or Secondary Education Establishments
UNIVERSITA DEGLI STUDI DI FERRARA
Italy
EU contribution
€ 681 608,75
Address
Via Ariosto 35
44121 Ferrara
Activity type
Higher or Secondary Education Establishments
E.P.O.S. IASIS RESEARCH AND DEVELOPMENT LTD
Cyprus
EU contribution
€ 528 800
Address
Kosti Palama 34 Aspelia Diam 5
1096 Lefkosia
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
TAMPEREEN KORKEAKOULUSAATIO SR
Finland
EU contribution
€ 583 318,75
Address
Kalevantie 4
33100 Tampere
Activity type
Higher or Secondary Education Establishments