Publications
A complete up-to-date list of publications of Robert can be found on and full-texts might be available from the .
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Great collaboration started by David Rand and Francis L茅vi with contributions from many including MRC DTP PhD students Laura Usselmann and Vadim Vasilyev, we describe a novel tool to interrogate the circadian clock from a single sample's transcriptome. We show in many examples how this can deliver useful information not only on the phase of the biological clock in the sample, but also give an estimate on the functionality of the clock. Furthermore, we show how this has potential as a biomarker to stratify data-sets from human tissues as well as inform research in experimental models. The TimeTeller algorithm will be available for use to any interested colleague soon. |
Previously as a preprint (), now peer-reviewed out in ACS Sensors. A collaboration led bt J茅r么me Charmet and Holosensor Medical Technology Ltd. introducing a new flow rate independent way to trap and then process circulating tumour cells. One stop shop from engineering of the device including simulating the flow conditions to making and testing as proof of principle and then application in a clinical data-set.
Previously a preprint , now out in iScience:
Great collaboration with Aarti Jagannath's lab in Oxford.
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Sleep and circadian rhythm disruption (SCRD), as encountered during shift work, increases the risk of respiratory viral infection including SARS-CoV-2. However, the mechanism(s) underpinning higher rates of respiratory viral infection following SCRD remain poorly characterised. To address this, we investigated the effects of acute sleep deprivation on the mouse lung transcriptome. Here we show that sleep deprivation profoundly alters the transcriptional landscape of the lung, causing the suppression of both innate and adaptive immune systems, disrupting the circadian clock, and activating genes implicated in SARS-CoV-2 replication, thereby generating a lung environment that promotes viral infection and associated disease pathogenesis. Our study provides a mechanistic explanation of how SCRD increases the risk of respiratory viral infections including SARS-CoV-2 and highlights therapeutic avenues for the prevention and treatment of COVID-19. |
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In a collaboration with Prof G眉ven from the University of Tasmania. CQ was widely used as oral antibiotic before removed from the market in many countries in 1970 after it was linked to subacute myelo-optic neuropathy (SMON) in Japan, leading to vision loss with many patients left wheelchair-bound. The toxic mechanism is not fullt explained yet. Given a re-emergence of CQ and related analogues as neuroprotectants, however, it is crucial to understand the underlying mechanism of CQ-induced toxicity to prevent any potential CQ-associated risks to future patients. We discovered that NQO1 protects cells against CQ toxicity in vitro and in vivo. Given the much higher prevalence of the inactivating C609T NQO1 polymorphism in the Japanese population compared to the European population, the results of this study suggest a rational for how the geographic restriction of SMON cases to Japan could be explained. Importantly, if CQ or its derivatives are to be used safely to treat neurodegenerative diseases, it seems imperative that NQO1 activity of prospective patients should be ascertained. |
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Stiffness matters in a size dependent manner, as found out by Dr Gurnani in a very enjoyable collaboration with Seb Perrier's group, and can now be read in "small" as Probing the effect of rigidity on the cellular uptake of core-shell nanoparticles: Stiffness effects are size dependent. The use of nanoparticles as vectors for the delivery of a wide range of biomedically relevant cargo is well established. Numerous studies have investigated the impact of size, shape, charge, and surface functionality of nanoparticles on mammalian cellular uptake. Rigidity, however, has been studied to a far lesser extent, and its effects are still unclear. Here, we systematically explore the importance of this property, and its interplay with particle size, using a library of core-shell spherical PEGylated nanoparticles synthesised by RAFT emulsion polymerisation. Rigidity of these particles was controlled by altering the intrinsic glass transition temperature (Tg) of their constituting polymers. Three different polymeric core rigidities were tested: hard, medium and soft using two particle sizes, 50 and 100 nm diameters. Cellular uptake studies indicated that softer particles are taken up faster and 3-fold more into mammalian cells compared to harder nanoparticles with the larger 100 nm particles. In addition, our study indicates major differences in the cellular uptake pathway, with harder particles being internalised through clathrin- and caveolae- mediated endocytosis as well as macropinocytosis, while softer particles were taken up by mainly caveolae- and non-receptor mediated endocytosis. However, our 50 nm derivatives did not show any appreciable differences in uptake efficiency suggesting that rigidity as a parameter in the biological regime might indeed be size dependent. |