Molecular Bionics

Giuseppe Battaglia | Group Leader / ICREA Research Professor
Azzurra Apriceno | Postdoctoral Researcher
Ian Peter Williams | Postdoctoral Researcher
Claudia Di Guglielmo | Laboratory Technician
Paula Magrinyà Aquiló | Masters Student
Gabriele Marchello | Visiting Researcher

About

In our labs, we 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 call this Molecular Bionics. Such an effort is multidisciplinary and involves inputs from chemistry, physics, material science and Engineering from one side and cell and molecular biology, physiology, immunology, oncology and neuroscience from the other.

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).

Membrane topology – Live fibroblast imaged after the delivery of PiP2 (green), Ceramide (white), Cholesterol (blue) and Actin (red) probes

Physical biology

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

Nanoscopic and biocompatible asymmetric polymer vesicles (known as polymersomes)

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.

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

News