Research Projects

International

NIH BICCN U01MH117023

“Imaging and Analysis Techniques to Construct a Cell Census Atlas of the Human Brain”

Starting date: 22-08-2018
End date: 31-05-2023

This project is funded by National Institutes of Health from United States in the context of the Brain Initiative Cell Census Network (https://biccn.org/) and proposes to create a multi-scale atlas for the human brain to map hemisphere-wide networks and also zoom in to see individual, labeled cells at micron resolution. This advance will be made possible through multiple imaging technologies, including light-sheet microscopy, tissue clearing, immunohistochemistry, magnetic resonance imaging, and newly-developed techniques in Optical Coherence Tomography. The ability to probe the cellular properties and multi-scale networks of specific areas in the human brain could evolve to an automated system for visualizing across the entire human brain in health and disease.
The project team is coordinated by the Massachuset General Hospital (PIs Bruce Fischl and David Boas) and supported by Icahn School of Medicine at Mount Sinai (co-PI Patrick Hof) and by European Laboratory of Non Linear Spectroscopy (co-PI Francesco Pavone).

Project Website

European

BadBUGS

“Quantitative measurement and imaging of drug-uptake by bacteria with antimicrobial resistance”

Starting date: 01-07-2016
End date: 30-06-2019

The innate resistance of Gram-negative bacteria to antibiotics and other antimicrobials is a consequence of combinatorial effects of their ability to efflux antibiotics out of the cell and their capacity to form antibiotic tolerant biofilms. There is an urgent need to quantitatively measure and image the localisation of antibacterial agents in bacteria and biofilms and to understand penetration and efflux processes. This will be achieved by developing innovative solutions for the label-free 3D imaging of antibacterial agents in bacteria, the traceable quantification of the vertical concentration profile of antibacterial agents in bacteria and biofilms, and for the real-time quantitative measurement of drug-uptake in bacteria and biofilms. Well-controlled model systems will also be developed to allow the cross-platform measurement of penetration, accumulation and efflux of antibacterial agents. Furthermore, novel signal enhancement strategies and advanced sample preparation methods for studying antibacterial agents will be created. Four biologically driven case studies will demonstrate the metrology breakthroughs to the healthcare, biomedical, pharmaceutical and medical device communities.
LENS will contribute to the project by developing optical solutions for super-resolution 3D imaging of bacteria and biofilms.
Project funded by EC H2020 programme.

Project Website

ERC - BrainBIT

“All-optical brain-to-brain behaviour and information transfer”

Starting date: 01-12-2016
End date: 30-11-2021

Exchange of information between different brains usually takes place through the interaction between bodies and the external environment. The ultimate goal of this project is to establish a novel paradigm of brain-to-brain communication based on direct full-optical recording and controlled stimulation of neuronal activity in different subjects. To pursue this challenging objective, we propose to develop optical technologies well beyond the state of the art for simultaneous neuronal “reading” and “writing” across large volumes and with high spatial and temporal resolution, targeted to the transfer of advantageous behaviour in physiological and pathological conditions.
We will perform whole-brain high-resolution imaging in zebrafish larvae to disentangle the activity patterns related to different tasks. We will then use these patterns as stimulation templates in other larvae to investigate spatio-temporal subject-invariant signatures of specific behavioural states. This ‘pump and probe’ strategy will allow gaining deep insights into the complex relationship between neuronal activity and subject behaviour.
To move towards clinics-oriented studies on brain stimulation therapies, we will complement whole-brain experiments in zebrafish with large area functional imaging and optostimulation in mammals. We will investigate all-optical brain-to-brain information transfer to boost an advantageous behaviour, i.e. motor recovery, in a mouse model of stroke. Mice showing more effective responses to rehabilitation will provide neuronal activity templates to be elicited in other animals, in order to increase rehabilitation efficiency. We strongly believe that the implementation of new technologies for all-optical transfer of behaviour between different subjects will offer unprecedented views of neuronal activity in healthy and injured brain, paving the way to more effective brain stimulation therapies.

Project funded by EC H2020 programme.
BrainBIT on Cordis

EuroBioimaging

Starting date: 2010
End date: 2018

The European Research Infrastructure for Imaging Technologies in Biological and Biomedical Sciences (Euro-BioImaging, EuBI or EuBI ERIC) provides open physical user access to a broad range of state-of-the-art technologies in biological and biomedical imaging for life scientists. In addition, EuBI will offer image data support and training for infrastructure users and providers. The EuBI consists of a set of 29 geographically distributed Node Candidates (specialised imaging facilities) that can grant access to scientists from all European countries and beyond. Currently, researchers can apply to use some of 36 imaging technologies offered through Euro-BioImaging. LENS is part of the Advanced Light Microscopy Italian Node.

Project Website

HBP SGA2

“Human Brain Project - Specific Grant Agreement 2”

Starting date: 01-04-2018
End date: 31-03-2020

The overall aim of the Human Brain Project (HBP) is to put in place a cutting-edge, ICT-based scientific research infrastructure, that will permit scientific and industrial researchers to advance our knowledge in the fields of neuroscience, computing and brain-related medicine.
In the Specific Grant Agreement 2 (SGA2), the HBP will build on the foundations it laid in the preceding Specific Grant Agreement 1 (SGA1). In that phase, it created initial versions of six separate ICT Platforms and made them available to external users. In SGA2, the HBP will extend the initial capabilities of these Platforms and transform them into an integrated scientific research infrastructure. The Neuroscience Subprojects will extend their research in brain organisation and theory to support the building of increasingly sophisticated models and simulations, as well as related work in brain-like computing and robotics, working up to replication of the whole mouse brain, while also laying the foundations for simulation of the much larger and more complex human brain.
The group involved in the HBP is the Biophotonics Group led by Francesco Saverio Pavone. The development and the application of new optical methodologies and the consequent acquisitions provide fundamental insights in the knowledge of the brain and his diseases and represent a completely new approach for the investigation of the physiology of neuronal network. LENS applies this approach in both mouse (SP1) and human (SP2) subprojects in which he’s involved. Furthermore, LENS will follow the guidance of some simulation developments on HBP Platforms through the Co-Design Project 1 (CDP1).

Here below two videos related to main activities performed at LENS during the previous Specific Grant Agreement (SGA1), ended in March 2018:
Anna Letizia Allegra Mascaro - Multi-scale investigation of brain machinery with correlative microscopy

Giacomo Mazzamuto - Mazzamuto Giacomo - A software pipeline for efficient processing of 3D high-resolution microscopy images on large-brain samples

The two videos are realized by the HBP Education Programme Office in the context of HBP Student Conferences.

Project funded by EC H2020 programme.

Project Website

Laserlab-BIOAPP

Starting date: 01-12-2015
End date: 30-11-2019

The Joint Research Activity BIOAPP will pursue three main objectives addressing key developments of innovative workstations and methodologies.
These range from the investigation of single bio-molecules and single cells to in-vivo microscopy on living animals to the development of biomaterials and diagnosis tools for human diseases.
Three main topics are addressed by BIOAPP:
• Bioimaging and biosensing
• Bio-materials
• Translational research
LENS is involved in the bioimaging and biosensing area and in Translational research.
Project funded by EC H2020 programme.

Project Website

N2B-patch

“Nose to Brain Delivery of BIIB033 via the Olfactory Region for the Regenerative treatment of Multiple Sclerosis Using Novel Multi-functional Biomaterials Combined with a Medical Device”

Starting date: 01-01-2016
End date: 31-12-2019

The project objective is the development of an innovative nose to brain (N2B) drug delivery technology. This will be achieved with the development of a biomaterial-based innovative formulation that will be applied with the aid of an endoscope and a medical device assembly as a matrix patch to the nasal olfactory region for the chronic treatment of Multiple Sclerosis (MS). LENS will monitor the correct delivery, integrity and cellular interaction of the drug.
Project funded by EC H2020 programme.

Project Website

PICCOLO

“Multimodal highly-sensitive PhotonICs endoscope for improved in-vivo COLOn Cancer Diagnosis and clinical decision support”

Starting date: 01-01-2017
End date: 31-12-2019

The multidisciplinary PICCOLO team proposes a new compact, hybrid and multimodal photonics endoscope based on Optical Coherence Tomography (OCT) and Multi-Photon Tomography (MPT) combined with novel red-flag auto-fluorescence technology for in vivo diagnosis and clinical decision support. By combining the outstanding structural information from OCT with the precise functional information from MPT, this innovative endoscope will provide gastroenterologists immediate and detailed in situ identification of colorectal neoplastic lesions and facilitate accurate and reliable in vivo diagnostics , grading capabilities for colon cancer as well as in-situ lesion infiltration grading and margin assessment. With the development of compact instrumentation, the cost of the components and thus the system will be significantly reduced. Human representative animal models will be used to generate imaging biomarkers that allow automated detection, assessment and grading of disease. The developed system will be tested in operating room conditions.
Project funded by EC H2020 programme.

Project Website

National

NanoMAX

Starting date: 01-12-2013
End date: 31-12-2018

In vitro diagnostics (IVD) is one of the areas of biomedicine and, in general, biotechnology, with the highest rates of international development. In Italy there are resources, historical knowledge, and new initiatives to derive innovation both in technology and content.
The establishment of a network of laboratories and companies in the sector is a necessity for the development of coordinated and mutually reinforcing priorities in the field of nanoscience and nanotechnology. The chances of success of nanotechnology in the biomedical field, and to compete on the international level, is influenced both by the creation of a critical mass, on the other hand the ability to integrate skills and disciplines in technology (materials technology, ITC , automation, miniaturization, microelectronics, advanced optics, etc) with skills and experience in leading biomedical field (molecular biology, genetics, microbiology, oncology, etc.).
The existing consortium project Nanomax pursues the realization of ultra-sensitive sensor platform aimed at the quantitative detection of biomarkers of cancer (breast cancer, colorectal cancer) and viral (hepatitis C virus HCV and its mutants) in biological fluids. The platform will be developed in Nanomax prototype configurations of increasing complexity and integration. The evolution of technology is guided by criteria of scalability to the demonstration of a point-of-care (POC) development. Several detection schemes (optical, mechanical, electrical) state of the art are explored in the current project.

MIMIC - All-optical brain imaging and control in freely moving rodents

Starting date: 01-01-2018
End date: 31-12-2022

The goal of the present project is to develop innovative optical methods for imaging, control, and, ultimately, the transfer of neural activity patterns in freely moving rodents. Current methods for monitoring and controlling neural activity across large areas of the cerebral cortex are based on conventional microscopy techniques and require head-fixation of the rodent.
This precludes the study of neural dynamics associated to complex behaviors such as spatial exploration and the social interactions. We want to overcome the state of the art by developing a miniaturized, wide-field optical system to be mounted on the head of the animal, to monitor and control neural activity (MIMIC). For imaging purposes we will explore two strategies: one based on a lens-free system with OLED illumination and sCMOS image sensors; the other based on a miniaturization of an optical microscope with lenses. The imaging system will be integrated with an array of optical fibers coupled with microprisms for multispot optogenetic stimulation. Each MIMIC will be mounted on the head of mice that express fluorescent indicators of neural activity and photosensitive channels for the optogenetic stimulation, the goal beeing to study the relationship between neural activity and behavior in freely moving animals. The behavioral tasks will be performed in an virtual reality (VR)-based arena, in which the action of the subject determines a specific sensitive stimulation. Said VR arena will be developed combining touchscreen technologies and an immersive environment, in which we will study how cortical activity correlates with two domains of animal behavior, i.e., motor control and social interactions.
The potentials of MIMIC in monitoring and controlling neural activity will be exploited to transfer pattern of neural activity between freely behaving mice, with the ambitious goal of transferring pattern associated with optimal behavioral performances. This revolutionary approach will be employed to explore the possibility of improving rehabilitation in a mouse model of cortical stroke, with the idea of transferring activity pattern from subjects who show a positive response to rehabilitation training to less responsive mice. In conclusion, we believe that the approach proposed here for monitoring and control of neural activity could have a great impact in the fields of photonics and neurosciences. The results of our project could allow to drastically increase, in quantitative terms, the output of experimental data, to contribute to the study of the central nervous system in more naturalistic contexts, to advance technologies for the communication between nervous systems, and lastly to lay the ground for more effective neurorehabilitative strategies.

Project funded by Italian Ministry of Research (MIUR) under the FARE programme.


Regional

Gliomics

“Proteomica/genomica/metabolomica per l’individuazione di biomarcatori e lo sviluppo d una piattaforma di rivelazione ultrasensibile in fluidi corporei periferici: applicazione al glioblastoma multiforme”

Starting date: 17-03-2017
End date: 16-03-2019

Early diagnosis of brain pathologies is hampered by the lack of specific biomarkers that can be detected in the blood during routine checks. This is mainly due to the presence of the brain blood barrier (BBB) ​​that isolates the brain from the rest of the body. Consequently, all putative biomarkers that can spread outside BBB pass it only in small quantities. The glioblastoma is a rare disease (GBM) which is a clear example of this situation. Although there is currently no technology that allows early diagnosis of the disease, a number of putative markers have been identified: their detection after diagnosis would be a useful tool to monitor the evolution of the tumor during treatment, providing valuable prognostic information on response to a given therapy. In this project, we will promote the convergence between clinical, genomic / proteomic, molecular cell biology and nanotechnology to develop a new pioneering ultrasensitive device for the detection of biomarkers, both new and already known, for GBM in peripheral fluids.
Project funded by Tuscany Region, programme FAS - Salute

ECRF-P4

“Sistemi innovativi di imaging ottico e analisi dell’immagine per la caratterizzazione di network neuronali alterati in pazienti pediatrici affetti da malformazioni focali dello sviluppo corticale”

Starting date: 01-01-2017
End date: 31-12-2019

Project funded by Ente Cassa di Risparmio di Firenze


Past Projects

ECRF-P1

Nuove tecnologie ottiche per la diagnosi istopatologica di tumori solidi, funded by Ente Cassa di Risparmio di Firenze

ECRF-P2

Imaging multispettrale nel THz e nel Medio Infrarosso per la diagnosi istopatologica, funded by Ente Cassa di Risparmio di Firenze

ECRF-P3

Caratterizzazione delle cascate di segnalazione e di trascrizione indotte dall’interazione membrane-amiloide

ECRP

Diagnostic technology for the post-operative monitoring of pediatric brain tumors, funded by Ente Cassa di Risparmio di Pisa

EUTrigTreat

Cardiac arrhythmias: from genes to improved management of patients, funded by EC FP7

FIRB

Sviluppo di una piattaforma per lo studio della meccanotrasduzione: dalla singola molecola alla cellula vivente, funded by Italian Ministry of Research Futuro in Ricerca

FIRC

Polarized cell structures in metastasis: coordination of the plasma, membrane, cytoskeleton and organelles. Funded by the Fondazione Italiana per la Ricerca sul Cancro (FIRC).

HBP RUP

FLAGSHIP Human Brain Project Ramp-Up-Phase (RUP) - FP7

HBP SGA1

FLAGSHIP Human Brain Project - Specific Grant Agreement 1 (SGA1) - H2020

LITE

Development of advanced laser imaging techniques for the anterior and posterior eye, funded by ERANET Biophotonics+

LightPatch

Led Technology in Photo Haemostasis, funded by ERANET Biophotonics+

SALUS

Automated digital scanning and diagnosis of tissues using multimodal non-linear optical microscopy

Stem Cells

New Animal Model, Nanotechnologies and Neuroimaging to Study Interactions and Homing of Human Neural Stem Cells in Stroke. Funded by the Italian Ministry of Health

ToRSADE

Monitoraggio e prevenzione delle morti improvvise cardiache giovanili in Toscana