About the Project
• This is a truly multidisciplinary project spanning atmospheric science, physical chemistry and cryopreservation: it features a unique blend of simulations and experiments, leveraging the cutting-edge facilities offered by the University of Warwick and providing the opportunity for the student to develop a unique set of research skills.
• A world-leading research environment featuring some of the best people working on ice, such as Prof. David Quigley and Dr. Thomas Whale, both based in Warwick and thus directly available to maximise the impact of the project. On top of that, the student will hugely benefit from the ice-related research ongoing in both the Sosso and the Gibson groups, with strong ties to both industrial partners and academic collaborators in the UK and overseas.
• A cutting-edge approach aimed at tackling a long-standing issue in atmospheric science, with important reverberations for the healthcare sector due to the relevance of the formation of ice in biological matter. As such, there is the opportunity to make a real impact, by unravelling the microscopic details responsible for the formation of “biological ice” in the atmosphere – and in our own cells as well!
The formation of ice is a process of paramount importance for atmospheric science, as it impacts the structure and the dynamics of e.g. mixed-phase clouds (Atkinson et al., 2013; Murray, 2017; Slater et al., 2015). Strikingly, water almost always needs the help of some foreign substance to transform into ice: while inorganic materials such as minerals or clays have been traditionally associated with the formation of ice (Kiselev et al., 2017), recent evidence indicates that biological systems such as bacterial fragments play a key role in facilitating the occurrence of "biological" ice in the atmosphere (Christner et al., 2008; Pratt et al., 2009; Hoose et al., 2010; O’Sullivan et al., 2015).
In fact, the formation of ice in biological matter is also crucial for cryopreservation and medical applications (John Morris and Acton, 2013; Jang et al., 2017) - and yet, we still do not know what is it that makes e.g. a certain bacterial fragment so efficient (or not!) in promoting the formation of ice. This is because the time- and length-scales involved with this process are awfully small/short (nano-seconds and nano-meters, respectively!) so that even state-of-the-art experiments struggle to achieve the necessary resolution we need to characterize this process.
In this project, we are going to unravel the origin of ice nucleation on bacterial fragments as well as some synthetic counterparts of them - some biomimetics (Congdon et al., 2015; Biggs et al., 2017), useful to pinpoint specific structural features of e.g. the cell walls. To this end, we will leverage a unique combination of computer simulations (Fitzner et al., 2019, 2015; Sosso et al., 2018) and experimental techniques (Deller et al., 2015; Casillo et al., 2017) spanning multiple time and length scales, from the atomistic details of hydrogen bonding to the ice nucleating ability of whole libraries of bacterial fragments, cell walls, and biomimetics.
This multidisciplinary approach harnesses the ice-related expertise of PI and Co-I, both based at the University of Warwick, to provide the student with an exceptional blend of skills, delivering a cutting-edge piece of research with the potential to transform our understanding of biological ice in the atmosphere. In addition, we envisage this proposal to also impact the current paradigm of cryopreservation, which relies on the challenging control of ice in our cells (Jang et al., 2017).
This project features a mixture of simulations (Dr. Sosso, Co-I) and experiments (Prof. Gibson, PI).
Simulations of ice formation (nucleation and growth) (Fitzner et al., 2015; Sosso et al., 2018; Fitzner et al., 2019)in the presence of atomistic models of cellular membranes and cell walls will be performed by means of molecular dynamics simulations (Understanding Molecular Simulation, 2002). The relevant training and facilities will be provided by the research group of Dr. Sosso.
The molecular-level insight obtained will be leveraged to design splat assays (Deller et al., 2014) and frozen droplet experiments (Whale et al., 2015) aimed at quantifying the ice nucleating ability of different classes of bacterial fragments and selected biomimetics. These experiments will be performed under the supervision of Prof. Gibson.
Cryo-TEM as well as complementary biophysical techniques will also be used to gain further insight into the mechanism and kinetics of ice formation in bacterial fragments.
Biggs, C.I., Bailey, T.L., Graham, Stubbs, C., Fayter, A., Gibson, M.I., 2017. Polymer mimics of biomacromolecular antifreezes. Nature Communications 8, 1546. https://doi.org/10.1038/s41467-017-01421-7
Casillo, A., Parrilli, E., Sannino, F., Mitchell, D.E., Gibson, M.I., Marino, G., Lanzetta, R., Parrilli, M., Cosconati, S., Novellino, E., Randazzo, A., Tutino, M.L., Corsaro, M.M., 2017. Structure-activity relationship of the exopolysaccharide from a psychrophilic bacterium: a strategy for cryoprotection. Carbohydr Polym 156, 364–371. https://doi.org/10.1016/j.carbpol.2016.09.037
Christner, B.C., Morris, C.E., Foreman, C.M., Cai, R., Sands, D.C., 2008. Ubiquity of Biological Ice Nucleators in Snowfall. Science 319, 1214–1214. https://doi.org/10.1126/science.1149757
Congdon, T., Dean, B.T., Kasperczak-Wright, J., Biggs, C.I., Notman, R., Gibson, M.I., 2015. Probing the Biomimetic Ice Nucleation Inhibition Activity of Poly(vinyl alcohol) and Comparison to Synthetic and Biological Polymers. Biomacromolecules 16, 2820–2826. https://doi.org/10.1021/acs.biomac.5b00774
Deller, R.C., Vatish, M., Mitchell, D.A., Gibson, M.I., 2015. Glycerol-Free Cryopreservation of Red Blood Cells Enabled by Ice-Recrystallization-Inhibiting Polymers. ACS Biomater. Sci. Eng. https://doi.org/10.1021/acsbiomaterials.5b00162
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