Ana Grenha

Afiliación:

Facultade de Ciências e Tecnologia, Universidade do Algarve,Centro de Ciências do Mar,Portugal

Título:

The potential of inhalation in therapeutics

Abstract:

Pulmonary drug delivery is gathering considerable attention nowadays, benefiting from the fact that the lung may be used as a port of entry of drugs aimed at either local or systemic effect. On one side, lung delivery of drugs is attractive to address local lung diseases, which is currently the major application of the delivery route. In this context, apart from conventional approaches on asthma or chronic obstructive pulmonary disease (COPD), other respiratory diseases are now seeing scientific efforts translating into therapeutic solutions that involve drug inhalation, such as cystic fibrosis, tuberculosis, pneumonia or lung cancer. The possibility to concentrate the drug where needed, providing the co-localisation of drugs and action sites, with the consequent decreased systemic exposure and diminished side-effects, is certainly beneficious in this regard. On the other side, the lung also displays anatomical and structural characteristics that potentiate the use of this route for the delivery of systemically acting drugs. Such beneficial characteristics include the large surface area (~100 m2) that is available for drug absorption, high vascularisation and low metabolic activity comparing with other routes of delivery [1]. Some biopharmaceutical drugs are now finding their application through inhalation. In parallel to promising therapeutic approaches, the lung route may also play a role in immunisation strategies, which is of particular interest for immunisation against airborne diseases [2]. Regardless the purpose, deliver drugs/antigens to or through the lung implies working out a formulation complying with specific requisites to reach the desired site of action. Therefore, formulation is key in the development of successful lung drug delivery strategies.

In this lecture, the beneficial properties of the lung for drug delivery applications will be presented, along with the challenging characteristics that drive the design of suitable inhalable drug carriers. Potential applications of this route for the treatment/prevention of respiratory diseases will be highlighted, with particular focus on tuberculosis therapy and immunisation strategies. In the end, the audience is expected to deepen the knowledge on the abilities of the lung route for the delivery of drugs, be conscious about the inherent challenges and aware of the potential of inhalable therapies.

Aitziber Lopez Cortajarena

Afiliación:

Biomolecular Nanotecnology group of CIC-BiomaGUNE

Título:

"Protein-nanomaterial engineered composites: a new horizon for biologic drugs and diagnostic tools"

Abstract:

The treatment and diagnosis of many diseases still remain a challenge. Inspired by nature, we explore biomolecules and their derivatives as novel therapeutic/diagnostic agents. Among biomolecules, proteins rise huge interest due to their high versatility, biocompatibility, and biodegradability. In particular, we use a class of engineered repeat proteins, the consensus tetratricopeptide repeat (CTPR) proteins due to their stability and robustness as a base scaffold that can be easily tailored to endow desired functions to the protein. For example, the introduction of metal-binding residues (e.g., histidines, cysteines) drives the coordination of metal ions and the subsequent formation of nanomaterials.[1] Additionally, new binding capabilities can be encoded within the CTPR unit or this can be conjugated with other peptides/proteins.[2] These properties allow the development of protein-nanomaterial composites.[2,3] Generally, the fusion of two distinct materials exploits the best properties of each, however, in protein-nanomaterial composites, the fusion takes on a new dimension as new properties arise. These composites have ushered the use of protein-based nanomaterials as biopharmaceuticals beyond their original therapeutic scope and paved the way for their use as theranostic agents. In this context, engineered proteins have emerged as promising scaffolds to hold simultaneously therapeutic and diagnostic functions, as has been recently demonstrated in our pioneering in vitro and in vivo examples.

David Brea

Afiliation:

Champalimaud Foundation, Lisbon, Portugal

Title:

Brain-immune interactions in stroke: a two-way pathway.

Abstract:

Stroke is a “brain attack”, that occurs when blood flow to an area of the brain is interrupted. When this happens, brain cells are deprived of oxygen/glucose and begin to die. When brain cells die, abilities controlled by that are of the brain such as memory, speech, or motor control are lost. Stroke pathophysiology involves a series of complex events including excitotoxicity, calcium overload, oxidative stress, and apoptosis. These mechanisms trigger an important immune/inflammatory reaction, characterized by the activation of microglia (immune cell resident in the brain), the release of cytokines and the infiltration of peripheral immune cells.

An important source of immune cells may be the intestinal compartment, one of the largest immune organs in the body, where immune cells are “educated” by the continuous interaction with commensal microbes. Therefore, we investigated the effects of intestinal flora on the immune system and the outcome after cerebral ischemia. We were able to show a novel microbiota-immune-brain axis that is based on the observation that the alteration of intestinal microbiota (dysbiosis) induces a profound remodeling on the intestinal immune system. This remodeling is characterized by the expansion of an anti-inflammatory cell subtype, namely Regulatory T cells, and the suppression of a pro-inflammatory cell subtype, namely IL-17+ γδ T cell. Our data suggest that, after stroke, T cells are able to traffic from the intestine to the Central Nervous System, localized in the meninges and increase neuroinflammation by secreting IL-17. IL17 is a proinflammatory cytokine that triggers the production of other mediators resulting in the infiltration of additional immune cells with a cytotoxic phenotype, and contributing, in this way to the stroke pathophysiology.

Based on these data, one could expect that anti-inflammatory/immunomodulatory therapies may be a good option for stroke treatment. However, so far, inhibition of inflammatory response (for example with IL-1R blockers), blocking leukocyte infiltration (for example with natalizumab), or treatments with pleiotropic immunomodulators (eg, allogeneic adult stem cells) have been unsuccessful on treating stroke in patients. Part of these failures is because stroked brain communicates with the peripheral immune system inducing what is called post-stroke immunosuppression. This immunosuppressive response of peripheral immunity contributes to post-stroke infections and other important secondary effects that will be reviewed during this talk and that compromise stroke outcome at short and long term.

Natalia Vilor-Tejedor

Afiliación:

BarcelonaBeta Brain Research Center, Barcelona, Spain. Center for Genomic Regulation, Barcelona, Spain. Erasmus University Medical Center, Rotterdam, Netherlands.

Title:

A random walk down in Imaging Genetic studies

Abstract:

The complexity of neurodegenerative diseases is not only apparent from their clinical presentation, but it is also corroborated by a range of preclinical and experimental studies. To identify which underlying molecular pathways are relevant in neurodegenerative processes, big data has been successfully exploited leading to many insights into their pathophysiology. For instance, the study of genetic factors and their combined action with brain features can help us to determine biological mechanisms in stages prior to the appearance of symptomatology. Specifically, there has been a particular interest in the integrative analysis of genetic data with neuroimaging information (framework known as “imaging genetics”), which represents a current advance for the development and improvement of diagnosis and personalized medicine of complex neurological diseases (Medland et al., 2022). Polygenic risk scores (PRS) are extremely useful in this context. PRSs combine the individual effect of each genetic variant in a single score that summarizes the genetic predisposition of each individual to a specific disorder/condition. The quantification of genetic scores will be useful to explore the association between the elevated genetic predisposition of a certain disease and candidate brain features related to neurodegeneration, in people without traditional risk factors. This strategy will help to further understand biological processes related to individual genetic predisposition, years before neurological symptoms appear, and thus will help to promote preventive practices and interventions. Another strategy consists of analysing both multivariate neuroimaging and genetic data to better capture the complex relationships that may exist between different biological levels. An example of this strategy is the application of the multiple factorial analysis and its extensions (Vilor-Tejedor et al., 2019). The inclusion of the multivariate perspective provides an improvement in the statistical power and predictive capacity in IG studies. Finally, novel work is focused on considering whether the genetic predisposition to complex disorders is associated with the joint modulation of specific brain features (Vilor-Tejedor, et al., 2021).

Alexander Govorov

Afiliation:

Physics and Astronomy Department, Ohio University

Title:

Plasmonic Metastructures and Bio-Assemblies for Optics and Photochemistry: Chirality, DNA-origami, and hot electrons

Abstract:

Plasmonic nanostructures and metamaterials are very efficient at the absorption and scattering of light. The studies to be presented in this talk concern special designs of hybrid nanostructures with electromagnetic hot spots, where the electromagnetic field becomes strongly enhanced and spatially concentrated. Overall, plasmonic nanostructures with hot spots demonstrate strongly amplified optical and energy-related effects, and this talk will review some of such phenomena. Using nanoparticle arrays made of different metals, one can transfer plasmonic signals coherently and with minimal losses. Plasmonic hot spots efficiently generate energetic electrons, which can be used for photochemistry and photodetection. Nanostructures with small interparticle gaps can strongly enhance heat's optical generation and confine high photo-temperatures in small volumes. Colloidal nanocrystal assemblies and metastructures with plasmon resonances allow us to strongly enhance the chiral optical responses (circular dichroism) of biomolecules and to induce chiral photo-chemical effects.

Ramón Reig

Afiliation:

Instituto de Neurociencias UMH-CSIC

Title:

Synchronization of multisensory information in dorsomedial striatum

Abstract:

How the brain operates with different sensory discrepancies is an essential question in order to understand how visual and somatosensory perturbations engage motor responses. The basal ganglia (BG) are involved in motor functions. The striatum is the input layer of the BG and receives cortical projections from sensory, motor and associative areas and thalamus. The rodent’s dorsal striatum is functionally subdivided in two regions; the lateral and medial striatum (Alegre-Cortes et al. 2021). The 95% of the striatal neurons are GABAergic projection neurons called MSNs. They are divided into two subpopulations according to their axonal projections and their different dopamine receptor expression, defining the direct and indirect pathway. In addition, the striatum is massively innervated by dopaminergic axons from the substantia nigra pars compacta. Dopamine is known to play a role in processes leading to corticostriatal synapses, modulating and inducing changes in synaptic transmission and plasticity. Single neurons in the dorsomedial striatum (DMS) are excited by tactile and visual inputs, thus processing information from different modalities. We studied how dopamine modulates the integration of this bimodal information in mouse DMS, as well as its effect on spontaneous activity. We obtained in vivo whole-cell recordings from identified medium spiny neurons (MSNs) during presentation of tactile, visual and simultaneous bimodal stimuli in resting conditions or after DA-induced release. Our results show that DA induces the synchronization of bimodal information specifically in direct pathway MSNs Altogether, our results propose a new mechanism underlying multisensory integration mediated by DA release.

David Ruano

Afiliation:

Centro de Astrobiología (INTA-CSIC)

Title:

Protein microarrays for a highly sensible detection of anti-SARS-CoV-2 antibodies in serum.

Abstract:

Protein microarrays are a tool to identify target molecules on a solid surface. In our group we have ample expertise in the analysis of environmental samples with this technique using SOLID, an instrument that can process regolith and detect whether bacterial strains, specific proteins and/or small molecules are present. During the Covid19 pandemic, we have applied this knowledge to the development of SCOVAM, a fluorescence-linked immunosorbent assay with several viral antigens (spike, nucleocapsid, main protease Nsp5) of SARS-CoV-2 as capturing probes in a fluorescence immunoassay for COVID-19 serological testing. Given its specificity and sensitivity, we will further apply this technology to monitor the health status of astronauts during spaceflight, which suffer harsh living conditions due to stress, radiation, or a closed environmen.

This work has been funded by INTA’s internal budget, the Spanish Ministry of Science and Innovation grant nos. RTI2018-094368-B-I00, and MDM-2017-0737 (Excelencia ‘María de Maeztu’ to Centro de Astrobiología), the ‘Programa de Atracción de Talento’ of the local Government of Madrid and the CSIC project number 202020E079.

Riccardo Marin

Afiliation:

UAM (Madrid)

Title:

Silver sulfide nanocrystals for imaging and sensing: A Bildungsroman

Abstract:

Fluorescence imaging affords real-time images of biological tissues in a safe, non-invasive way thanks to the use of non-ionizing radiation (i.e., photons) both as the probe and the collected signal. The use of photons translates also to the need for a relatively inexpensive imaging setup that is easy to operate – being composed, in its simplest form, of a laser source and a photodetector. This is in stark contrast with established methods like computed tomography, magnetic resonance, and positron emission tomography, which require expensive and cumbersome equipment, sometimes employing ionizing radiation. Although fluorescence imaging could rely on the autofluorescence of endogenous tissue components, the use of luminescent species as contrast agents greatly improves the performance of this imaging technique. In this vein, luminescent nanoparticles have emerged as ideal candidates to act as fluorescence imaging contrast agents. Among them, silver sulfide nanocrystals have recently become the prime choice, owing to their benign chemical composition, near-infrared emission, and brightness. Moreover, their sensitiveness to temperature changes enables gathering information about the thermal state of biological systems. In this talk, silver sulfide nanocrystals will be presented as one of the most promising contrast agents for fluorescence imaging. After discussing synthesis strategies and methods to increase the brightness of these nanocrystals, their applications at the preclinical level will be presented. Challenges lying ahead and possible research directions will also be highlighted.