RealHOPE

Titolo: Real World Handling of Protein Drugs - Exploration, Evaluation and Education

Acronimo: RealHOPE

Bando: European Commission – Horizon 2020 – SOCIETAL CHALLENGES - Health, demographic change and well-being

Durata: 4 anni

Responsabili scientifiche: Giorgia Miolo, Patrizia Polverino de Laureto

Budget totale: 272.500 €

Abstract:
Innovative protein drugs, genetically engineered versions of human proteins, have the capacity to cure previously incurable diseases. However, they are sensitive due to their complex structure. For instance, they react to shaky transportation or being left beside a sunny window by patients. The EU-funded RealHOPE project will measure real-life events during drug handling by applying smart tag technologies. It will also conduct focus interviews with personnel in hospital pharmacies, clinics and with patients and caregivers to understand current handling practice and what the desired handling instructions and limitations are. These insights will be used to design in use mimicking stability protocols for protein drugs and ultra scaled-down devices for stability assessment.

  BINC

Titolo: Exploring the role of enteric nervous system on myelination during early life: modulation of gut microbiota to prevent neuropsychiatric disorders

Acronimo: BINC (Biostime Institute for Nutrition and Care)

Bando: European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 722717

Durata: 1 anno

Responsabile scientifico: Prof. Maria Cecilia Giron

Budget totale: 50.000,00 €

Abstract:
The enteric nervous system (ENS) is an extensive neuronal network, embed in the gastrointestinal (GI) tract, that holds sensing machinery for monitoring luminal microbiota-derived perturbations. Since GI microbial colonization and central nervous system (CNS) development occur during a critical window in neonatal life, exposure to dysbiotic events, such as stress or infection in infancy, can disrupt the development of microbiota-gut-brain (MGB) axis, leading to neuropsychiatric disorders (NPDs; e.g., major depressive disorder (MDD), autism spectrum disorders (ASD)). Most neural axons are unmyelinated at birth. During infancy oligodendrocytes ensure rapid myelination, that slowly consolidates spatiotemporally until adulthood to ensure neurotransmission. The prefrontal cortex, undergoing later myelination in newborn, is affected by neonatal intestinal dysbiosis, and highly implicated in NPDs. Intriguingly, the ENS expresses myelin and contains glial cells that share transcriptome features of oligodendrocytes, supporting the hypothesis that ENS is involved in the neuroinflammatory process that disseminates to the CNS. Whether and how NPDs involve the gut is of increasing importance given emerging reports that NPDs are transmitted from the gut to the brain. We found that antibiotic-induced dysbiosis or TLR2/TLR4 deficiency in mice leads to significant morphofunctional ENS changes and altered myelinization, characterized by modified gut motility and susceptibility to neuroinflammation which can be rescued by intraperitoneal administration of GDNF or TLR2 agonists. Following on these findings, we posit that gut dysbiosis causes enteric myelinization changes similar to those seen in NPDs, resulting in ENS neuroinflammation, altered GI motility and impaired cognition, and depends on host-microbiota interactions. The proposed multidisciplinary study will integrate the science of neurogastroenterology with neuropsychopharmacology. This hypothesis will be tested with three aims performed in the cuprizone mouse model. First, we will evaluate whether cuprizone administration causes enteric disrupted myelinization, neuroimmune changes and neuronal loss. Second, we will assess whether disruption in gut motility precedes impaired cognition. Finally, using experimental manipulation of the microbiota, we will explore the role of host-microbiota interactions in NPDs-associated GI disease and their relationship to cognition. Specifically, we will examine whether and how NPDs progression is affected by antibiotic-mediated dysbiosis, or TLR2 stimulation. Successful completion of the proposed studies will identify critical pathophysiological pathways that affect the gut and precede the onset of NPDs. The results will inform novel prevention and intervention strategies for NPDs and cognitive dysfunction during infancy.

  Ocuther

Titolo: Educational Network in Ocular Drug Delivery and Therapeutics

Acronimo: OcuTher

Bando: European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 722717

Durata: 4 anni

Responsabile scientifico: Prof. Paolo Caliceti

Budget totale: 516.122,00 €

Abstract:
Ocular drug development has transformed from niche area to a major field in drug development in which many companies, including European big pharma has entered recently. Ocular drug development is a unique field in terms of drug targets and end-points of activity, local drug administration routes, tissue barriers and pharmacokinetics, drug delivery and formulation challenges and local toxicity issues. These issues are slowing down the development of drugs for the unmet needs in ophthalmology. The main objective of the project is to educate experts of preclinical ocular R&D to facilitate the success of European pharmaceutical industry and research community. This objective will be reached by joining forces of the leading European academic and industrial researchers in ophthalmology, materials science and nanomedicine, drug delivery and targeting, and systems pharmacology. We shall educate 15 Early Stage Researchers in a network where they will receive tailored, multi-disciplinary and inter-sectoral education in preclinical ocular drug development. The thesis projects are directed to the drug treatment of retinal diseases, the major challenge in the field. The project combines new drug candidates from the experts of ophthalmology, innovative drug delivery technologies from pharmaceutical scientists and companies, and modern in vitro, in silico and in vivo methods from various partners. The thesis projects include secondments in academic and industrial partner laboratories and course programme that encompasses the relevant fields in ocular drug development. Therefore, this project presents unique combination of innovation and education in the field with obvious need for such education. The ESRs and other outcomes of this project will greatly benefit the future competitiveness of European science and industry in this field of expanding importance.

  BICEPSvsHIV

Titolo: Novel strategies for anti-HIV-1 therapy: Small molecules targeting RNA partners of the nucleocapsid protein

Acronimo: BICEPSvsHIV

Bando: European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant - H2020-MSCA-IF-2016 - No. 751931

Durata: 2 anni

Responsabile scientifico: Prof. Barbara Gatto, Prof. Alice Sosic

Budget totale: 164.203,00 €

Abstract:
European Commission considers HIV/AIDS as a top priority and significantly invests in research devoted to the development of alternative therapeutic strategies leading to new antiretrovirals, which are urgently needed to overcome the emergence of resistance to existing drugs. The “BICEPSvsHIV” project proposes a novel and innovative strategy that draws the spotlight on RNA. Specific RNA sequences of the viral genome are substrates of the HIV-1 nucleocapsid (NC), a highly conserved protein known for promoting remodeling of nucleic acid structures in essential steps of the virus replication cycle. The proposed strategy consists in the employment of bis-3-chloropiperidines (BICEPS) as RNA cross-linking agents able to freeze selectively the tridimensional conformations of the RNA partners of NC, thus impairing its activities. RNA is a challenging molecule from the medicinal chemistry perspective, but the rewards it can yield are invaluable. The Experienced Researcher (ER) will work at The RNA Institute (SUNY Albany) during the outgoing phase, aimed at 1) the elucidation of BICEPS detailed molecular mechanism of reaction towards RNA and 2) the identification of BICEPS targeting selectively the RNA substrates of NC. During the incoming phase at the University of Padova (UNIPD), the achievements will be translated into 3) the thorough biological evaluation of the in vitro NC inhibition by BICEPS, leading to 4) the identification of anti-NC lead compounds. The project provides the ER with an outstanding training-through-research opportunity by means of a personalized multidisciplinary project, in which the ER will enlarge her scientific profile with new excellent skills. The training includes both scientific and transferable skills, aimed at the reinforcement