Dr Andrea Rocco

Biography

I graduated in Physics at the University of Pisa (Italy) in 1994, discussing a thesis in quantum field theory. In 1998 I obtained my PhD in Physics from the University of North Texas (USA), where I focused on the role of stochastic processes in classical and quantum mechanical systems.

Between 1998 and 2007 I held postdoctoral positions at the University of Barcelona (Spain), the University of Rome "La Sapienza" (Italy), CWI (The Netherlands), and the University of Oxford (UK). During this period of time, I made a gradual transition from the general fields of statistical mechanics and pattern formation towards the modelling of biological systems. In 2007 I obtained a Lectureship in Applied Mathematics at the University of Bath (UK), where I taught mathematical biology modules at both MSc and undergraduate levels.

In 2009 I joined the University of Surrey (UK) as Research Fellow in Systems Biology, and was appointed Lecturer in Mathematical Biology in 2012.

Research Interests

As a theoretical physicist, my research focus has primarily been within the general fields of statistical mechanics, nonlinear dynamics, and pattern formation. In recent years, I have made a transition towards the study of biological systems, for which I adopt a variety of theoretical methodologies borrowed from physics and mathematics, such as dynamical systems theory and the theory of stochastic processes.

The objective of my current research is two-fold. On the one hand, I aim to explain biological data by mathematical analysis and computational approaches. On the other hand, I aim to use biological data to explore the boundaries of physics, and assess the potential and the limitations of a physics-inspired framework to describe living matter.

My main research lines are the following:

Stochastic effects in subcellular networks
Molecular networks, such as gene regulatory networks or metabolic networks, are affected by stochastic fluctuations. Fluctuations due to low copy numbers of proteins, or to gene expression bursts, define so-called intrinsic noise, while fluctuations originating in the environment are usually referred to as extrinsic noise. This part of my research concerns the study of both intrinsic and extrinsic noise, and of their interplay. In particular, extrinsic noise can have highly non-trivial and counterintuitive effects, which may lead to noise-induced transitions [“Systems Biology of Tuberculosis”, Springer (2013)]. Consideration of these effects has led me to introduce the concept of stochastic control in metabolic networks [Phys. Biol. (2009)], where noise itself is proven to be able to act as a control mechanism that tunes metabolic concentrations and fluxes. I am now interested in the principles underpinning noise propagation across different layers of regulation in metabolic and gene networks.

Ergodicity breaking in isogenic bacterial populations
Stochastic fluctuations are at the base of much of the variability that we see in biology. Different phenotypes are well known to arise in populations of genetically identical cells in the same environment. It is an intriguing conjecture that this variability is evolutionarily selected for. Yet, what precisely its origin is remains an unanswered question. The requirement that distinct phenotypes be observable over typical experimental times suggests that they result from static heterogeneities in the population, which randomly distinguish individual cells from each other. I am investigating the possibility that such static heterogeneities are in fact produced by the stochastic bursting activity of gene expression, supplemented with specific mechanisms capable of slowing down fluctuations. To explain this mechanism in general terms, I have recently introduced in the context of bacterial growth the concept of ergodicity breaking, borrowed from statistical mechanics and dynamical systems theory [PLoS ONE (2013)]. This is a useful framework to explain how dynamical noise at the single cell level may become a static heterogeneity at the population level. I have applied this framework to investigate the emergence of growth phenotypes in clonal populations of bacterial cells.

Models of bacterial persistence
Ergodicity breaking in isogenic bacterial populations points to a novel explanation of the phenomenon of so-called bacterial persistence, or drug tolerance. Bacterial persistence is the phenomenon by which a clonal population of bacterial cells exposed to antibiotics is initially killed very rapidly, and then very slowly. The same model that accounts for the emergence of distinct growth phenotypes by ergodicity breaking [PLoS ONE (2013)], accounts also for much of the phenomenology observed in persistence. This discovery is based on the well-known dependence of antibiotic killing on cellular growth rate, and is now being tested experimentally (collaboration with the group of Prof Johnjoe McFadden, University of Surrey). If validated, it will have major implications for developing strategies for controlling persistent infections.

Dynamics of cell differentiation
A problem conceptually related to explaining the emergence of distinct phenotypes in isogenic populations, is to explain the emergence of different cell types from multipotent stem cells. In collaboration with Prof Robert Kelsh (University of Bath), we have constructed the first core gene regulatory network describing stable differentiation of melanocytes in zebrafish [PLoS Genetics (2011)]. I have developed the mathematical aspects of the project, by using a combination of mathematical analysis and simulations. I am now interested in assessing the role played by noise, both intrinsic and extrinsic, in the dynamics of the differentiation process.

Biofilm formation
In my group, we are also investigating biofilm formation and quorum sensing. Biofilms are communities of different species of microbes embedded within a matrix of extracellular polymeric substance, and adhering to a surface. They constitute a major challenge when treating bacterial infections. We are constructing a mathematical model to investigate multi-species dynamics within biofilms, and their response to different antimicrobial agents. We are exploring the possibility that altering intercellular communications may control the balance of the present species, and favour antimicrobial efficacy. The mathematical predictions are tested against in vitro and in vivo data from upper respiratory tract biofilms (collaboration with the groups of Prof Roberto La Ragione and of Dr Jennifer Ritchie, Surrey, and with Mr San Sunkaraneni, NHS), and if validated, will suggest novel strategies for the treatment of infections complicated by biofilm formation. This project is supported by MILES (Models and Mathematics in Life and Social Sciences - EPSRC) and the University of Surrey.

Past research
In the past, I have been involved in the study of branching of gas discharges (so-called streamers), and in the development of the related description in terms of conformal mapping techniques [see for instance Plasma Sources Sci. Technol. (2006) for a review]. I also studied the effect of extrinsic noise on the propagation of reaction-diffusion fronts. In the case of the so-called Fisher Equation (FKPP), I contributed to identifying the anomalous sub-diffusive behaviour characterizing the front position [Phys. Rev. E (2000)], and to generalize it through the definition of a new roughness universality class for travelling waves in 2 bulk dimensions [Phys. Rev. Lett. (2001)]. In the context of off-equilibrium statistical mechanics, I also addressed fundamental issues on complexity reduction in models for glasses [J. Chem. Phys. (2000)]. During my PhD, I developed fractional calculus techniques to study fractal phenomena in both space and time [Physica (1999); Phys. Rev. E (1999)].

Publications

Cellular differentiation

• E.R. Greenhill, A. Rocco, L. Vibert, M. Nikaido, R.N. Kelsh
  An Iterative Genetic and Dynamical Modelling Approach Identifies Novel Features of the Gene Regulatory Network Underlying Melanocyte Development
  PLoS Genetics 7, e1002265 (2011)
  doi: 10.1371/journal.pgen.1002265
  Full text is available at: http://epubs.surrey.ac.uk/710804/

Stochasticity in subcellular networks

• A. Rocco, A.M. Kierzek, J. McFadden
  Slow protein fluctuations explain the emergence of growth phenotypes and persistence in clonal bacterial populations
  PLoS ONE 8, e54272 (2013)
  doi: 10.1371/journal.pone.0054272
  Full text is available at: http://epubs.surrey.ac.uk/749321/
• A. Rocco, A.M. Kierzek
  Stochastic effects in metabolic pathways
  In "Encyclopedia of Systems Biology", Eds. W. Dubitzky, O. Wolkenhauer, H. Yokota, K.-H. Cho, Springer (2013)
• A. Rocco, A.M. Kierzek, J. McFadden
  Stochastic gene expression in bacterial pathogens: A mechanism for persistence?
  In "Systems Biology of Tuberculosis", Eds. J. McFadden, D. Beste, A. Kierzek, Springer (2013)
  
• A. Rocco
  Stochastic control of metabolic pathways
  Phys. Biol. 6, 016002 (2009)
  doi: 10.1088/1478-3975/6/1/016002
  Full text is available at: http://epubs.surrey.ac.uk/710801/

Molecular Evolution

• G. Lunter, A. Rocco, N. Mimouni, A. Heger, A. Caldeira, J. Hein
  Uncertainty in Homology Inferences: Assessing and Improving Genomic Sequence Alignment
  Genome Res. 18, 298 (2008)
  doi: 10.1101/gr.6725608
  Full text is available at: http://epubs.surrey.ac.uk/710803/

Low temperature plasmas

• U. Ebert, C. Montijn, T.M.P. Briels, W. Hundsdorfer, B. Meulenbroek, A. Rocco, E.M. van Veldhuizen
  The multiscale nature of streamers
  Plasma Sources Sci. Technol. 15, S118 (2006)
• B. Meulenbroek, A. Rocco, U. Ebert
  Streamer branching rationalized by conformal mapping techniques
  Phys Rev. E 69, 067402 (2004)
  doi: 10.1103/PhysRevE.69.067402
  Full text is available at: http://epubs.surrey.ac.uk/240038/
• U. Ebert, B. Meulenbroek, C. Montijn, A. Rocco, and W. Hundsdorfer
  Spontaneous branching of anode-directed streamers: conformal analysis and numerical results
  Proceedings of the XXVI International Conference on Phenomena in Ionized Gases [refereed]
  Greifswald, Germany, July 15-20, 2003
• U. Ebert, A. Rocco, W. Hundsdorfer, and M. Arrayás
  A mechanism for streamer branching
  Proceedings of ESCAMPIG 16th - ICRP 5th (Joint European-Japanese Conference on Gas Discharges) [refereed]
  Grenoble, France, July 14-18 2002
• A. Rocco, U. Ebert and W. Hundsdorfer
  Branching of Negative Streamers in free flight
  Phys. Rev. E 66, 035102 (2002)
  doi: 10.1103/PhysRevE.66.035102
  Full text is available at: http://epubs.surrey.ac.uk/240039/

Glassy dynamics

• B. Coluzzi, A. Crisanti, E. Marinari, F. Ritort, A. Rocco,
  A New Method to Compute the Configurational Entropy in Spin Glasses
  Eur. Phys. J. B 32, 495 (2003)
• A. Crisanti, F. Ritort, A. Rocco, and M. Sellitto
  Is the Stillinger and Weber decomposition relevant for coarsening models?
  J. Phys.: Condens. Matter 14, 1523 (2002)
• A. Crisanti, F. Ritort, A. Rocco, and M. Sellitto
  Inherent Structures and non-equilibrium dynamics of 1D constrained kinetic models: A comparison study
  J. Chem. Phys. 113, 10615 (2000)

Pattern Formation

• A. Rocco, L. Ramírez-Piscina, J. Casademunt
  Kinematic reduction of reaction-diffusion fronts with multiplicative noise: Derivation of stochastic sharp-interface equations
  Phys. Rev. E 65, 056116 (2002)
  doi: 10.1103/PhysRevE.65.056116
  Full text is available at: http://epubs.surrey.ac.uk/240040/
• A. Torcini, A. Vulpiani, A. Rocco
  Front propagation in chaotic and noisy reaction diffusion systems: A discrete-time map approach
  Eur. Phys. J. B 25, 333 (2002)
• A. Rocco, J. Casademunt, U. Ebert, and W. van Saarloos
  Diffusion coefficient of propagating fronts with multiplicative noise
  Phys. Rev. E 65, 012102 (2002)
• G. Tripathy, A. Rocco, J. Casademunt, and W. van Saarloos
  Universality class of fluctuating pulled fronts
  Phys. Rev. Lett. 86, 5215 (2001)
  doi: 10.1103/PhysRevLett.86.5215
  Full text is available at: http://epubs.surrey.ac.uk/240041/
• F.X. Magdaleno, A. Rocco, J. Casademunt
  Interface dynamics in Hele-Shaw flows with centrifugal forces: Preventing cusp singularities with rotation
  Phys. Rev. E 62, R5887 (2000)
• A. Rocco, U. Ebert, and W. van Saarloos
  Subdiffusive fluctuations of "pulled" fronts with multiplicative noise
  Phys. Rev. E 62, R13 (2000)
  doi: 10.1103/PhysRevE.62.R13
  Full text is available at: http://epubs.surrey.ac.uk/240042/

Macroscopic manifestations of randomness

• P. Grigolini, A. Rocco and B.J. West
  Fractional Calculus as a Macroscopic Manifestation of Randomness
  Phys. Rev. E 59 2603 (1999)
• A. Rocco and B.J. West
  Fractional Calculus and the Evolution of Fractal Phenomena
  Physica A 265, 535 (1999)
• A. Rocco and P. Grigolini
  The Markov approximation revisited: Inconsistency of the standard quantum Brownian motion model
  Phys. Lett. A 252, 115 (1999)
• P. Allegrini, P. Grigolini, A. Rocco
  Slow motion as a thermal gradient effect
  Phys. Lett. A 233, 309 (1997)

Teaching

BMS1023 - Chemistry and Maths for the Biosciences

BMS3072 - Systems Biology: Genomes in action