Biostructures

Biostructures

Engineering protein molecules that self-assemble into complex bioarchitectures is an innovative goal of nanobiotechnology. We aim to generate novel bioinspired protein scaffolds that can self-assemble upon stimulation into desired well-ordered and stable multicomponent nanobiostructures, such as biomolecular cages and biocrystals. This process is strongly driven by specific technological needs. Applications can range from design of bioactive 3D nanobiomaterials and nanobiosensors, to designed biomedicines. My research interests also focus on the relationships biostructure/interactions/function of innovative membrane protein targets relevant for metabolic and neurological disorders, and the discovery of privileged chemicals as leads to novel drugs.

Primary research tools include approaches of protein engineering, recombinant protein overexpression in mammalian and bacterial cell systems, production scale-up, biocrystallization, and structural biophysics analyses (mainly x-ray crystallography, single particle cryo-electron microscopy, small angle x-ray scattering and neutron scattering, surface plasmon resonance and isothermal titration calorimetry, supported by computational approaches). Overall, these methods provide insights into protein structure and dynamics at the atomic level, and allow us to characterize the thermodynamics and kinetics of protein interactions. Findings result in key parameters for efficient protein architecture design, and discovery of novel target modulators and drug leads.

The group of BIOSTRUCTURES has equipped laboratories of biochemistry, biophysics and cell biology, for the production and purification of proteins, their crystallization and characterization. We use highly sensitive, high-throughput and label-free techniques to study non-covalent biomolecular interactions, including surface plasmon resonance (SPR SensìQ Pioneer) and isothermal titration calorimetry (Microcal Auto-ITC200). The lab is supported by a facility of mass spectrometry and peptide solid-phase synthesis. We have access to major European Synchrotron Radiation Facilities, including ESRF (Grenoble), DIAMOND (Oxford) and ELETTRA (Trieste).

IIT Publications List

Publications
2021
Margheriti F., Chiaruga S., Martino E., De Lorenzi V., Marotta R., Frank G.A., Garau G.
Cryo-EM analysis of membrane NAPE-PLD associated to nanodiscs
2nd Italian Crystallographic Association Biological MacroMolecules Group Meeting
2021
Sestito S., Bacci A., Chiarugi S., Runfola M., Gado F., Margheritis E., Gul S., Riveiro M.E., Vazquez R., Huguet S., Manera C., Rezai K., Garau G., Rapposelli S.
Development of potent dual PDK1/AurA kinase inhibitors for cancer therapy: Lead-optimization, structural insights, and ADME-Tox profile
European Journal of Medicinal Chemistry, vol. 226
2021
Martino E., Chiarugi S., Margheriti F., Garau G.
Mapping, Structure and Modulation of PPI
Frontiers in Chemistry, vol. 9
2021
Hoelzgen F., Zalk R., Alcalay R., Schwartz S.G., Garau G., Shahar A., Mazor O., Frank G.A.
Neutralization of the anthrax toxin by antibody-mediated stapling of its membrane penetrating loop
bioRxiv
2021
Hoelzgen F., Zalk R., Alcalay R., Cohen-Schwartz S., Garau G., Shahar A., Mazor O., Frank G.A.
Neutralization of the anthrax toxin by antibody-mediated stapling of its membrane-penetrating loop
Acta Crystallographica Section D: Structural Biology, vol. 77, pp. 1197-1205

Collaborations

Collaborations
  • Gabriel A Frank, Ben-Gurion University of the Negev, Israel.

  • Alexander Dityatev, DZNE - Center for Neurodegenerative Diseases, Germany.

  • Antimo Gioiello, University of Perugia, Italy.

  • Simona Rapposelli, University of Pisa, Italy.

  • Dr Ranieri Bizzarri & Riccardo Nifosì, CNR-Nano - Scuola Normale Superiore, Pisa, Italy.

Journal cover

Journal cover
Chemical Biology