Molecular Bionics

Giuseppe Battaglia | Group Leader / ICREA Research Professor
Azzurra Apriceno | Postdoctoral Researcher
José Rui Pereira | Postdoctoral Researcher
Lara Aiassa | PhD Student
Claudia Di Guglielmo | Laboratory Technician

 

 

About

We are chemists, physicists, mathematicians, engineers, biologists who work alongside to design bionic units that mimic specific biological functions and/or introduce operations that do not exist in Nature. We apply a constructionist approach where we mimic biological complexity in the form of design principles to produce functional units from simple building blocks and their interactions.​ We called such an approach: Molecular Bionics.

 

We are engaged in several activities involving the synthesis and characterisation of novel hierarchal materials whose properties are the result of the holistic combination of its components:

Molecular engineering

We combine synthetic and supramolecular chemistry to tune inter/intramolecular interactions and self-assembly processes to form dynamic soft materials whose molecular, supramolecular and mesoscale structures are tuned and fit for the final application (pictured right: molecular engineering of nanoscopic structures starting from molecule passing to polymers and finally to supra molecular structures).

 

Physical biology

Figure 1 Giant polymersomes formed by 2D printing (Howse et al Nature Materials 2009)

Our materials are designed to interact with living systems and thus its biological activity is studied in high detail. We have developed and established new methodologies to study living systems and how synthetic materials interact with them combining holistically physical and life sciences (Physical Biology).

 

Synthetic biology

Figure 2; The brain vasculature (red) of a mouse surronded by astrocytes (cyan) and neurons (white) (Matias-Lorenço et al in preparation )

Both know-hows are applied to study biological organisation and complexity creating synthetic surrogates that act as models, as well as to engineer novel sophisticated ways to interact with living organisms.

 

Somanautics

In analogy to medical bionics, where engineering and physical science converge to the design of replacement and/or enhancement of malfunctioning body parts, we take inspiration from viruses, trafficking vesicles and exosomes to apply molecular engineering to create nanoscopic carriers that can navigate the human body (Somanautics) with the final aim to improve drug delivery or create new diagnostic tools.

Visit our external website to find out more.

Projects

Publications

Donnelly, Joanna L., Offenbartl-Stiegert, Daniel, Marín-Beloqui, José M., Rizzello, Loris, Battaglia, Guiseppe, Clarke, Tracey M., Howorka, Stefan, Wilden, Jonathan D., (2020). Exploring the relationship between BODIPY structure and spectroscopic properties to design fluorophores for bioimaging Chemistry - A European Journal 26, (4), 863-872

Designing chromophores for biological applications requires a fundamental understanding of how the chemical structure of a chromophore influences its photophysical properties. We here describe the synthesis of a library of BODIPY dyes, exploring diversity at various positions around the BODIPY core. The results show that the nature and position of substituents have a dramatic effect on the spectroscopic properties. Substituting in a heavy atom or adjusting the size and orientation of a conjugated system provides a means of altering the spectroscopic profiles with high precision. The insight from the structure–activity relationship was applied to devise a new BODIPY dye with rationally designed photochemical properties including absorption towards the near-infrared region. The dye also exhibited switch-on fluorescence to enable visualisation of cells with high signal-to-noise ratio without washing-out of unbound dye. The BODIPY-based probe is non-cytotoxic and compatible with staining procedures including cell fixation and immunofluorescence microscopy.

Tian, Xiaohe, Angioletti-Uberti, Stefano, Battaglia, Giuseppe, (2020). On the design of precision nanomedicines Science Advances 6, (4), eaat0919

The blood-brain barrier is made of polarized brain endothelial cells (BECs) phenotypically conditioned by the central nervous system (CNS). Although transport across BECs is of paramount importance for nutrient uptake as well as ridding the brain of waste products, the intracellular sorting mechanisms that regulate successful receptor-mediated transcytosis in BECs remain to be elucidated. Here, we used a synthetic multivalent system with tunable avidity to the low-density lipoprotein receptor–related protein 1 (LRP1) to investigate the mechanisms of transport across BECs. We used a combination of conventional and super-resolution microscopy, both in vivo and in vitro, accompanied with biophysical modeling of transport kinetics and membrane-bound interactions to elucidate the role of membrane-sculpting protein syndapin-2 on fast transport via tubule formation. We show that high-avidity cargo biases the LRP1 toward internalization associated with fast degradation, while mid-avidity augments the formation of syndapin-2 tubular carriers promoting a fast shuttling across.

Tian, Xiaohe, Leite, Diana M., Scarpa, Edoardo, Nyberg, Sophie, Fullstone, Gavin, Forth, Joe, Matias, Diana, Apriceno, Azzurra, Poma, Alessandro, Duro-Castano, Aroa, Vuyyuru, Manish, Harker-Kirschneck, Lena, Šarić, Zhang, Zhongping, Xiang, Pan, Fang, Bin, Tian, Yupeng, Luo, Lei, Rizzello, Loris, Battaglia, Giuseppe, (2020). On the shuttling across the blood-brain barrier via tubule formation: Mechanism and cargo avidity bias Science Advances 6, (48), eabc4397

The blood-brain barrier is made of polarized brain endothelial cells (BECs) phenotypically conditioned by the central nervous system (CNS). Although transport across BECs is of paramount importance for nutrient uptake as well as ridding the brain of waste products, the intracellular sorting mechanisms that regulate successful receptor-mediated transcytosis in BECs remain to be elucidated. Here, we used a synthetic multivalent system with tunable avidity to the low-density lipoprotein receptor–related protein 1 (LRP1) to investigate the mechanisms of transport across BECs. We used a combination of conventional and super-resolution microscopy, both in vivo and in vitro, accompanied with biophysical modeling of transport kinetics and membrane-bound interactions to elucidate the role of membrane-sculpting protein syndapin-2 on fast transport via tubule formation. We show that high-avidity cargo biases the LRP1 toward internalization associated with fast degradation, while mid-avidity augments the formation of syndapin-2 tubular carriers promoting a fast shuttling across.

Gouveia, Virgínia M., Rizzello, Loris, Nunes, Claudia, Poma, Alessandro, Ruiz-Perez, Lorena, Oliveira, António, Reis, Salette, Battaglia, Giuseppe, (2019). Macrophage targeting pH responsive polymersomes for glucocorticoid therapy Pharmaceutics 11, (11), 614

Glucocorticoid (GC) drugs are the cornerstone therapy used in the treatment of inflammatory diseases. Here, we report pH responsive poly(2-methacryloyloxyethyl phosphorylcholine)–poly(2-(diisopropylamino)ethyl methacrylate) (PMPC–PDPA) polymersomes as a suitable nanoscopic carrier to precisely and controllably deliver GCs within inflamed target cells. The in vitro cellular studies revealed that polymersomes ensure the stability, selectivity and bioavailability of the loaded drug within macrophages. At molecular level, we tested key inflammation-related markers, such as the nuclear factor-κB, tumour necrosis factor-α, interleukin-1β, and interleukin-6. With this, we demonstrated that pH responsive polymersomes are able to enhance the anti-inflammatory effect of loaded GC drug. Overall, we prove the potential of PMPC–PDPA polymersomes to efficiently promote the inflammation shutdown, while reducing the well-known therapeutic limitations in GC-based therapy.

Keywords: Inflammation, Macrophages, Glucocorticoid, Polymersomes

Equipment

  • State-of-the-art facilities for cell culture including 5 class A cell cabinets: one dedicated for LPS and RNAse free cell culture and one dedicated for infected tissues
  • Fluorescence Activated Cell Sorting (FACS)
  • Confocal microscope to perform live cell 4D imaging
  • Thermocycler
  • Real-time PCR
  • Automated Western Blot
  • Gel Permeation Chromatography
  • High-Performance Liquid Chromatography
  • Ultra Performance Liquid Chromatography equipped with fluorescence, UV/Vis and Infrared and light scattering detectors
  • Dynamic light scattering unit
  • Nanoparticle tracking analysis
  • UV and Fluorescence spectroscopy
  • Automated liquid handling units
  • Nanoparticle production units

Collaborations

  • Xavier Salvatella
    IRB Barcelona
  • Francesca Peiro
    Physics-University of Barcelona
  • Kostas Kostarellos
    Life Science- University of Manchester/ICN2
  • Giorgio Volpe
    Chemistry-UCL
  • Simona Parrinello
    Cancer Institute -UCL
  • Finn Werner
    Structural Biology -UCL
  • Nick Lane
    Evolutionary Biology -UCL
  • Darren Hargraves
    Pediatric Neuro-Oncology -UCL
  • Timothy McHugh
    Clinical Microbiology =UCL
  • Sebastian Brander
    Neurology -UCL
  • Joan Abbott
    Physiology -King’s College London
  • Molly Stevens
    Bioengineering -Imperial College London
  • Stefano Angioletti-Uberti
    Materials Science -Imperial College London
  • Ricardo Sapienza
    Physics -Imperial College London
  • Daan Frenkel
    Chemisty-University of Cambridge
  • Charlotte Williams
    Chemistry -University of Oxford
  • Francesco Gervasio
    Pharmacology -University of Geneve/UCL, UK
  • Francesco Stellacci
    Bionegineering -EPFL Switzerland
  • Tambet Tessalu
    Cancer Biology -University of Tartu (Estonia)/ Sanford Burnham Prebys Medical Discovery Institute
  • Darrel Irvine
    Bioengineering -MIT
  • Xiaohe Tian
    Life Sciences University of Anhui
  • Yupeng Tian
    Chemistry University of Anhui
  • Lei Luo
    Pharmacy -Southwest University, China
  • Kai Luo
    HuaXi hospital Sichuan University
  • Darren Hargrave
    Great Ormond Street Hospital, UCLH London
  • Sebastian Brander
    Queen Square National Centre for Neurology, UCLH London

News

Range selectivity, a new concept that could lead to more efficient nanoparticle drug delivery 

In a new study published in the scientific journal Nature Communications, researchers describe a new concept called “range selectivity”, explaining why biomimetic nanoparticles only bind to receptors when their density is within a precise range.

This finding could pave the way for the development of highly targeted therapies against a number of diseases.

Read more…

Bioengineering against the most resistant and deadly bacterial infections

An international team, led by Profs Giuseppe Battaglia and Loris Rizzello from the Institute for Bioengineering of Catalonia (IBEC), carried out out a study that opens the door to a new therapy capable of quickly and effectively eliminating infections caused by intracellular bacteria, the most resistant to immune defenses.

This therapy, based on synthetic vesicles, could considerably reduce the dose and duration of antimicrobial treatments, thus reducing the danger of generating resistance to antibiotics of pathogens such as those leading to tuberculosis.

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A “faster and safer” therapy against tuberculosis

A team of international scientists led by the Institute for Bioengineering of Catalonia (IBEC) has developed a “faster, more effective and safer” therapy to eliminate infections of intracellular bacteria that cause diseases such as tuberculosis. Scientists participating in the study include Group Leader Giuseppe Battaglia and the researcher Loris Rizzello of IBEC.

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IBEC researchers develop a model to design precision nanomedicine

Researchers at Institute for Bioengineering of Catalonia (IBEC) have proposed a model that gives important insights into how nanoparticles interact with cells, virus, bacteria or proteins, among others.

The findings provide a very powerful tool to design personalized nanomedicines, since allow the scientists to create nanoparticles tailor-made for each patient.

Read more…