ERC FUNDED PROJECTS

Hepatitis B virus (HBV) infections remain a major public health issue worldwide. Over 350 -400 million people are chronically infected by HBV, and about 1 million people die each year from the complications of this infection (cirrhosis and hepatocellular carcinoma) with a consequent hefty economic impact on national health systems. This led the World Health Organization to recognise HBV infection as a key priority and adopt the global health sector strategy to eliminate viral hepatitis, with a target of reducing new infections by 90% and mortality by 65% by 2030. The risk of developing a chronic infection in healthy adults is due to a weaker, dysfunctional and narrowly focused CD8+ T cell response. Since the mechanisms underlying HBV persistence are not fully elucidated, current treatments (antiviral drugs and Interferon) aim to reduce the development of liver disease, while a definitive treatment for curing this infection is not yet available on the market. Within the ERC Consolidator Grant 725038 “FATE”, we recently characterized the mechanisms behind the ineffective CD8+ T cell response towards HBV, demonstrating the potential efficacy of interleukin-2 (IL-2) – a cytokine – to reactivate it, thus achieving antiviral activity. This discovery, jointly with our proprietary third-generation, self-inactivating lentiviral vectors (LVs) that allow selective hepatocellular expression of IL-2, pave the way to single-dose gene therapy-based approach, a potential functional cure against chronic hepatitis B. 2LIVEr project intends to optimize and further validate our novel therapeutic approach from both a technical and commercial standpoint, moving from TRL3 to TRL4, thus fastening the roadmap towards the market.

150 000 €

Start date: 2020-07-01, End date: 2021-12-31

The applicant will collaborate with Irish, European and U.S.-based colleagues to develop a sustainable biorefinery and bioenergy industry in Ireland and Europe. The focus of this ERC Starting Grant will be the application of classical microbiological, physiological and real-time polymerase chain reaction (PCR)-based assays, to qualitatively and quantitatively characterize microbial communities underpinning novel and innovative, low-temperature, anaerobic waste (and other biomass) conversion technologies, including municipal wastewater treatment and, demonstration- and full-scale biorefinery applications. Anaerobic digestion (AD) is a naturally-occurring process, which is widely applied for the conversion of waste to methane-containing biogas. Low-temperature (<20 degrees C) AD has been applied by the applicant as a cost-effective alternative to mesophilic (c. 35C) AD for the treatment of several waste categories. However, the microbiology of low-temperature AD is poorly understood. The applicant will work with microbial consortia isolated from anaerobic bioreactors, which have been operated for long-term experiments (>3.5 years), and include organic acid-oxidizing, hydrogen-producing syntrophic microbes and hydrogen-consuming methanogens. A major focus of the project will be the ecophysiology of psychrotolerant and psychrophilic methanogens already identified and cultivated by the applicant. The project will also investigate the role(s) of poorly-understood Crenarchaeota populations and homoacetogenic bacteria, in complex consortia. The host organization is a leading player in the microbiology of waste-to-energy applications. The applicant will train a team of scientists in all aspects of the microbiology and bioengineering of biomass conversion systems.

1 499 797 €

Start date: 2011-05-01, End date: 2016-04-30

I aim to develop an X-ray imaging technique capable of filming processes in 3D, with a temporal resolution several orders of magnitude faster than up-to-date 3D X-ray imaging techniques. The unique penetration power of X-rays allows us to study systems in their native environment. This property has led to the development of X-ray microtomography (µCT). µCT acquires 3D information, which determines the functionality and mechanical properties of nature, by rotating a sample with respect to the X-ray source. µCT is a crucial tool for several scientific disciplines such as physics, biology, and chemistry. Over the last decade, µCT has become a technique capable of not only recording 3D information but also filming dynamical processes. Several breakthroughs have made this possible: i) intense X-ray sources (synchrotron light sources), ii) efficient and fast X-ray detectors, and iii) fast 3D reconstruction algorithms. Despite all of these developments, the acquisition protocols remain unchanged, i.e., the sample is only rotated faster. This fast rotation introduces forces which may alter the studied dynamics and ultimately limit the achievable temporal resolution. My project is to establish an X-ray microscope that avoids the sample rotation, obtaining 3D information from a single X-ray flash by splitting it into nine-angularly resolved beams which illuminate the sample simultaneously. This approach, when implemented at intense X-ray sources such as synchrotron light sources and X-ray free-electron lasers, will allow the filming of natural processes with micrometer to nanometer resolution and resolve dynamics from microseconds to femtoseconds. To demonstrate its capabilities, I will study fundamental processes in cellulose fibers, a renewable biomaterial, which can replace fossil-based materials, such as plastics. This technique will open up the possibility to film dynamics in 3D to answer questions coming from industry and natural sciences at rates not accessible today.

1 999 213 €

Start date: 2021-03-01, End date: 2026-02-28

MAPs are polymer-based composites that respond to magnetic fields with large deformation or tuneable mechanical properties. I aim to apply heterogeneous 3D printed MAPs as modifiable substrates to support biological structures which can have their deformation state and stiffness controlled by the external application of magnetic stimuli. Such mechanical stimulation has an important role on biological structures leading to alterations in functional responses, morphological changes and activation of growth or healing processes. Current bottlenecks preventing progress in this field are a lack of: a) appropriate experimental methodologies to enable characterisation of the behaviour of these materials; b) fundamental theoretical underpinnings to support the design and application of these new materials. The first step is to undertake in depth characterisation and assessment of 4D printed MAPs to create a detailed understanding of the underlying physics controlling the interactions between the polymeric matrices and embedded magnetic particles during application of mechanical and/or magnetic loadings. I will then culture biological structures on the novel 4D printed MAPs to create a ‘designed’ biostructure with specified and controllable responses to a given magnetic stimulus. These novel biostructures will be assessed using three applications: a) astrocyte cellular networks, b) neuronal circuits and c) astrocyte-neuronal networks. The evaluation of cellular damage, morphological and physiological alterations will validate the performance of the new biostructures and also contribute new understanding to the effects of deformation and stiffness gradients during glial scarring on physiological functions of central nervous system cells. The resulting deep understanding of magneto-mechanics of MAPs and their further development for controllable stimulation devices, will enable the international consolidation of my research group within the mechanics and bioengineering fields.

1 499 625 €

Start date: 2021-01-01, End date: 2025-12-31