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Professor Paola Borri

Professor Paola Borri

Professor, Coordinator of the European Marie Curie ETN consortium MUSIQ

School of Biosciences

School of Physics and Astronomy

Email
borrip@cardiff.ac.uk
Telephone
+44 (0)29 2087 9356
Fax:
+44 (0)29 2087 4116
Campuses
Sir Martin Evans Building, Museum Avenue, Cardiff, CF10 3AX
Users
Available for postgraduate supervision

Overview

Research activities in my group cover the area of biophotonics at the interface between life and physical sciences. In collaboration with the School of Physics and Astronomy, my research work includes:

  • development of next generation laser-scanning multiphoton microscopes based on Coherent Raman Scattering (CRS) for label-free studies on living cells and tissues
  • development of novel optical microscopy techniques for imaging and tracking single nanoparticles background free inside cells
  • development of optical biosensors for sensitive detection of biomolecules using plasmonics sensing with metallic nanoparticles or photonic cavities
  • time-resolved fluorescence resonance energy transfer (TR-FRET) as a probe of biomolecular interactions

See also our MUSIQ website for an update on the research within this EU consortium.

News

Fully-funded PhD studentship available to start in September 2022 within the BBSRC-funded SWBio DTP, project title "Developing a new bio-imaging tool for correlative light electron microscopy". 

See our research highlights recently published:

Interested in joining my lab as a self-funded post-graduate student or a postdoc/fellow?  Please contact me by email.

Biography

I did my undergraduate in Physics at the University of Florence (Italy) and then received the Laurea (MSc equivalent) summa cum laude and the Ph.D degree in Physics in 1993 and 1997 respectively. From 1997 to 1999 I was Assistant Research Professor at the Technical University of Denmark (Kgs.Lyngby, Denmark).

From 1999 to 2004 I worked as Senior Scientist and EU Marie Curie Fellow (2001-2003) at the Physics Department of Dortmund University in Germany where I received the Habilitation degree in Physics (Venia Legendi) in 2003. During this time I was interested in the experimental investigation of the optical properties of novel semiconductor nanostructures, such as quantum wells and quantum dots. In particular, I developed a new technique for the ultra-fast coherent laser spectroscopy of these nanostructures.

From September 2004 I moved to Cardiff University as Senior Lecturer. On August 1st 2007 I was promoted to Reader and on August 1st 2011 to a Personal Chair.

Honours and awards

In 2015 I received the Royal Society Wolfson Research Merit Award. Jointly funded by the Wolfson Foundation and the Department for Business, Innovation and Skills (BIS), the scheme aims to provide universities with additional support to enable them to attract science talent from overseas and retain respected UK scientists of outstanding achievement and potential.

I received the Marie Curie Excellence Award from the European Commission during the official award ceremony at the Ecole Polytechnique Federale de Lausanne on the 16th November 2006.

Marie Curie Excellence Awards (EXA) aim to give public recognition to outstanding past achievements of scientists who have reached a level of exceptional excellence in their given field. Up to five prizes of 50 000 Euros each are awarded every year.

Professional memberships

In 2010-2015 I was an EPSRC Leadership Fellow.

Since 2014 I am Fellow of the Learned Society of Wales.

Publications

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  • Gurioli, M.et al. 1998. Exciton formation and relaxation in GaAs epilayers. Physical Review B 58(20), pp. R13403-R13406. (10.1103/PhysRevB.58.R13403)
  • Langbein, W. W., Borri, P. and Hvam, J. M. 1998. Coherent exciton and biexciton nonlinearities in semiconductor nanostructures: effects of disorder. Presented at: 10th International Conference on Ultrafast Phenomena in Semiconductors, Vilnius, Lithuania, August-September 1998 Presented at Steponas, A. and Dargys, A. eds.Ultrafast Phenomena in Semiconductors: Proceedings of the 10th International Symposium on Ultrafast Phenomena in Semiconductors (10-UFPS), held in Vilnius, Lithuania, August/September 1998. Materials Science Forum Vol. 297-8. Zurich: Trans Tech Publications pp. 73-78.
  • Borri, P., Langbein, W. W. and Hvam, J. M. 1998. Ultrafast spectroscopy of semiconductor devices. Presented at: 10th International Symposium on Ultrafast Phenomena in Semiconductors, Vilnius, Lithuania, August-September 1998 Presented at Asmontas, S. and Dargys, A. eds.Ultrafast phenomena in semiconductors : proceedings of the 10th International Symposium on Ultrafast Phenomena in Semiconductors (10-UFPS), held in Vilnius, Lithuania, August/September 1998. Materials Science Forum Vol. 297-8. Zurich: Trans TechPublications pp. 67-71.

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Teaching

Module Lead of 4th-year Intergated Masters module "Advanced Research Methods"

Projects

Coherent Raman Scattering microscopy for label-free imaging of living cells and tissues

Optical microscopy is an indispensable tool for cell biology. Different microscopy methods are currently available and continuous effort is devoted to develop new techniques with improved sensitivity, selectivity and spatial resolution. An important issue in recent microscopy is the ability to perform non-invasive studies avoiding the need for fluorescent probes that are prone to photobleaching and can perturb the cell structure and function.

Together with Prof. Wolfgang Langbein in the School of Physics and Astronomy, we have developed a range of home-built laser-scanning multiphoton microscopes based on Coherent Raman Scattering (CRS), enabling rapid label-free chemically specific microscopy of living cells and tissues. A second-generation CRS microscope located in the School of Biosciences has been specifically built to perform multimodal correlative CRS, two -photon fluorescence (TPF) and second harmonic generation (SHG) microscopy for applications in cell biology. This system enables hyperspectral CRS acquisition which has led to the development of a quantitative image analysis tool to distinguish the composition of chemical components and retrieve their concentration and spatial distribution.

With these tools, we have determined the lipid uptake of fixed and living adipose derived human stem cells differentiating into pre-adipocytes, the lipid content and spatial distribution in live mammalian oocytes and early embryos, demonstrated a high-throughput high-content platform for drug screens, and quantitatively measured masses of lipids, proteins and DNA during cell division. We have also shown that CRS can be used to visualise single non-fluorescing nanodiamonds in cells for the first time (see Publications).

Resonant Four-Wave Mixing Imaging with gold nanoparticles

Imaging and tracking single nanoparticles using optical microscopy are powerful techniques with many applications in biology, chemistry, and material sciences. Applied methods to achieve contrast are dominantly fluorescence based, with fundamental limits in the emitted photon fluxes arising from the excited-state lifetime as well as photobleaching.

We have developed a new technique, based on four-wave mixing (FWM) interferometry, whereby single non-fluorescing gold nanoparticles (AuNPs) are imaged background-free even inside highly heterogeneous cellular environments, owing to their specific nonlinear plasmonic response, and their position is determined with nanometric precision in 3D. The technique is also uniquely sensitive to particle asymmetries of only 0.5% ellipticity, corresponding to a single atomic layer of gold, as well as particle orientation and chirality.

With this technique, we are investigating a number of AuNP-ligand-fluorophore conjugates and their integrity inside cells, using AuNPs as small as 5nm in radius and correlative FWM/confocal fluorescence imaging. The technique opens the prospect to an unprecedented level of understanding of the intracellular fate of single small AuNPs and their trafficking within complex 3D architectures inside living cells (see Publications).

Other research interests

  • Quantitative optical extinction microscopy of individual nano-objects
  • Ultrafast coherent dynamics of semiconductor quantum dot materials and devices
  • Optical biosensing by exploiting plasmonic resonances or photonic cavities
  • Time-resolved Förster Resonance Energy Transfer (TR FRET) as probe of biomolecular interactions

Grants

  • BBSRC, EPSRC, MRC, EU, Ministry of Defence – Dstl, DTI

Group members

  • Iestyn Pope, Research Associate (School of Biosciences, Cardiff)
  • Francesco Masia, Research Fellow (School of Biosciences, Cardiff)
  • Yisu Wang, Research Associate (School of Biosciences, Cardiff)
  • David Regan, Research Associate (School of Biosciences, Cardiff)
  • Barbara Santos Gomes, Research Associate (School of Biosciences, Cardiff)
  • Lukas Payne, Research Associate (School of Physics and Astronomy, Cardiff)
  • Samuel Hamilton, PhD student (School of Biosciences, Cardiff)
  • Dafydd Sion Harlow, PhD Student (School of Biosciences, Cardiff)
  • Zoltan Sztranyovszky, PhD Student (School of Physics and Astronomy, Cardiff)
  • Rhod Thomas, PhD student (School of Biosciences, Cardiff)
  • Nadhia Monim, PhD student (School of Biosciences, Cardiff)
  • Nicole Slesiona, MUSIQ ESR Fellow and PhD Student (School of Biosciences, Cardiff)
  • Vikramdeep Singh, MUSIQ ESR Fellow and PhD Student (School of Physics and Astronomy, Cardiff)
  • Martina Recchia, MUSIQ ESR Fellow and PhD Student (School of Biosciences, Cardiff)
  • Freya Turley, PhD Student (School of Physics and Astronomy, Cardiff)
  • Ozan Aksakal, PhD student (School of Biosciences, Cardiff)
  • Emily Lewis, PhD student (School of Biosciences, Cardiff)
  • Furqan Alabdullah, PhD student (School of Engeneering, Cardiff)

Collaborators

Supervision

I am interested in supervising PhD students in these research areas:

  • nonlinear laser micro-spectroscopy
  • label-free vibrational microscopy of living cells and tissues
  • imaging and tracking single nanoparticles in living systems
  • lipid membrane biophysics 

Project Examples:

Title: Sensing local biomolecular environments with coherent optical nanoscopy

The development of novel imaging tools and technologies, including super-resolution optical microscopy, has revolutionised our understanding of biology. Combining light microscopy with chemical sensing at the nanoscale in living cells holds the promise to unravel processes presently not accessible with existing techniques. For example, lipid nanodomains (rafts) are thought to have a key role in the way cytosolic membranes work in signalling and other important functions, and have attracted much attention in basic biology and disease research [1]. Although many experiments indicate their existence, lipid rafts remain controversial owing to their small size and the lack of suitable detection techniques in living cells. A related example is endocytosis, the process by which membrane lipids, proteins and extracellular content become internalised into the cell. There are several endocytic routes into the cell, each with a distinct protein machinery, cargos, and internalisation mechanisms [2]. Their characterization is crucial, beyond fundamental biology, for the design of drug delivery and therapeutic strategies. A combination of light microscopy with chemical sensing at the nanoscale would allow us to directly observe membrane lipid nanodomains in living cells and to define the localised biomolecular environment at single endocytic events occurring at the cell surface.

The main aim of this project is to demonstrate and quantify the applicability of novel optical microscopy techniques beyond state-of-the-art for local biosensing of biomolecules directly within living cells. Specifically, the aim is to exploit a unique combination of coherent anti-Stokes Raman scattering (CARS) [3] microscopy of endogenous biomolecules and Four-Wave Mixing (FWM) imaging of metallic nanoparticles [4]. The local field enhancement of CARS in the vicinity of a plasmonic nanoparticle will enable bio-sensing while the nanoparticle position is located with precision at the nanoscale by FWM [5]. A unique home-built CARS/FWM microscope is available in the supervisor’s laboratory [3-5], therefore the main emphasis of this project will be to push its applicability for sensing directly in living cells.

[1] https://doi.org/10.1194/jlr.TR120000658

[2] https://doi.org/10.1016/j.addr.2020.07.026

[3] http://dx.doi.org/10.1063/1.5027256

[4] http://dx.doi.org/10.1039/C9NR08512B

[5] http://dx.doi.org/10.1103/PhysRevX.7.041022

Title: Shedding new light on single protein-lipid membrane interactions

The interaction between proteins and lipid membranes is a fundamental process underpinning key functions in cell biology and the maintenance of life. Membrane proteins account for approximately 27% of the entire human proteome, and membrane receptors make up the largest group of drug targets in humans since they play a critical role in both infection and immunity [1]. Membranes are also the target for protein toxins produced by pathogens to attack cells from the outside and introduce perforations. Beyond their impact to human disease, toxins are of great interest in biotechnology, to control e.g. insect pests of agriculture [2]. Moreover, the challenge of antimicrobial resistance has ignited strong interest in antimicrobial peptides (AMPs) which form membrane-spanning pores as part of their bactericidal activity [3]. 

Despite the widespread importance of such systems, many key questions are still unanswered, including how do proteins remodel and diffuse within membranes in space and time? Where do they partition, depending on the heterogeneous lipid membrane chemical composition and curvature? How is the protein function modulated by the lipid environment at the atomic, molecular and long-range meso-scale? How is the lipid membrane local composition and curvature affected by the protein (an interplay often overlooked).

A major roadblock in achieving this understanding is the lack of suitable techniques capable of measuring single protein-lipid membrane interactions at the nanoscale with sub-millisecond time resolution, while keeping the system under observation in its intact natural state and without introducing structural-functional artefacts. Optical microscopy is a promising non-destructive and non-contact technique. However, to achieve the required sensitivity and specificity, presently it relies on tagging proteins and/or lipids, typically with fluorophores, which raises the question if the observed behaviour is real or artefactual [4].

The aim of this project is to contribute to the development and application of novel label-free optical imaging techniques to quantify the diffusion and partitioning of single proteins in physiologically relevant lipid membranes.

[1] https://doi.org/10.1038/nrd3478

[2] https://doi.org/10.3390/toxins6123296

[3] https://doi.org/10.3389/fcimb.2016.00194

[4] http://dx.doi.org/10.1038/nphoton.2015.251

Research Environment:  You will be exposed to a vibrant multi-disciplinary environment at the physics/life science interface.  You will join a well-funded academic team, with an outstanding track record of student supervision and publication output. The supervisory team offers a unique combination of expertise, with strong track records in developing novel optical microscopy techniques applied to life sciences. You will be immersed in a collaborative environment with expertise in the biology of lipid membranes and pore forming proteins, endocytosis and intracellular trafficking. 

Training and Development Opportunities: You will be trained in a variety of relevant techniques including advanced optical microscopy methods, fabrication of synthetic lipid membranes, and mammalian cell culture. You will develop the transferable skills of data analysis, communication and dissemination. The resulting skillset will boost your future employability both in academia and in industry. The supervisory team has strong links with companies, including microscope manufactures and image analysis software developers. Within this studentship, opportunities for visits/internships at these companies will arise. Global mobility opportunities will include visiting collaborating partner groups overseas, and participation to national/international conferences. The project will generate new knowledge and data that will be published in high quality journals. 

Areas of expertise

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