Daniel Rock Email & Phone Number

London Area, United Kingdom

* ER and oxidative stress assays* Compound screening* Target validation* CNS disease model characterisation* Assay Development

London, Greater London, United Kingdom

PhD work focuses on understanding the ageing process in neural stem cells and how we might apply this knowledge to slow down or rescue signs of cellular ageing through the action of novel anti-ageing compounds. To this end, an accelerated model of cellular ageing was generated in human neural stem cells based on expression of the pro-ageing protein, progerin, which recapitulates various hallmarks of physiological ageing related to DNA damage, senescence, loss of proteostasis and… Show more PhD work focuses on understanding the ageing process in neural stem cells and how we might apply this knowledge to slow down or rescue signs of cellular ageing through the action of novel anti-ageing compounds. To this end, an accelerated model of cellular ageing was generated in human neural stem cells based on expression of the pro-ageing protein, progerin, which recapitulates various hallmarks of physiological ageing related to DNA damage, senescence, loss of proteostasis and mitochondrial dysfunction. Using this model, existing anti-ageing compounds as well as novel clinically approved drugs were uncovered in a high-content drug screen based on recovery of lamin B1 levels and nuclear morphology. Top hits were able to rejuvenate aged neural stem cell function and one drug successfully extended C. elegans lifespan by 6%, highlighting the relevancy and translatability of the model to find novel anti-ageing candidates. As part of the iCASE PhD studentship, I had the good fortune to carry out an industrial placement in the labs at MSD UK, which is where high-content drug screening experiments were performed with the assistance of high-throughput liquid handling systems and automation. Show less

London Area, United Kingdom

1 year industrial placement in MSD UK Discovery Biology, Neuroscience, working at laboratories based at London Bioscience Innovation Centre as part of iCASE MRC DTP PhD programme.This placement facilitated execution of high-content drug screening of a diverse compound library using Tecan Fluent® 780 automated liquid handler and Opera Phenix Imaging System. Imaging data was analysed with Columbus/Harmony/Signals Image Artist pipelines.Additionally, many cell-based assays using… Show more 1 year industrial placement in MSD UK Discovery Biology, Neuroscience, working at laboratories based at London Bioscience Innovation Centre as part of iCASE MRC DTP PhD programme.This placement facilitated execution of high-content drug screening of a diverse compound library using Tecan Fluent® 780 automated liquid handler and Opera Phenix Imaging System. Imaging data was analysed with Columbus/Harmony/Signals Image Artist pipelines.Additionally, many cell-based assays using progerin ageing model established at King's College were validated at MSD UK. These were related to NSC ageing and neurodegeneration, and included: ROS (CellROX), oxidative stress (8-oxoG, NRF2 nuclear import), apoptosis & growth (Caspase 3-7 live-cell assay with Incucyte), proteostasis (OPP protein synthesis/SUnSET), DNA damage (H2AX), senescence (NFkB, laminB1, SA-beta-Gal), epigenetic dysregulation (H3K9me3) and mitochondrial/metabolic dysfunction (MitoStress, GlycoStress with Seahorse).Main achievements were the rediscovery of existing anti-ageing drugs (Fisetin, 17-DMAG, D+Q) in a lamin B1 recovery screening assay alongside several novel hits not previously associated with ageing. One drug in particular used in the treatment of rheumatoid arthritis recovered lamin B1 expression and corrected nuclear morphology deficits. This well-tolerated drug increased the lifespan of C. elegans worms by 6%, demonstrating the assay’s ability to find physiologically relevant compounds that counteract ageing and promote lifespan extension. Show less

Little Chesterford, Essex, United Kingdom

Research Projects: MesoBrain (https://www.mesobrain.eu/): a collaborative EU-funded project that aims to build a "brain on a chip", integrating defined iPSC-derived neural networks into a 3D scaffold to reproduce a physiologically relevant brain cortical module that displays in vivo connectivity and activity.My involvement in the project has been to generate functional iPSC-derived microglia that will be added to the cortical architecture, along with astrocytes and interneurons.… Show more Research Projects: MesoBrain (https://www.mesobrain.eu/): a collaborative EU-funded project that aims to build a "brain on a chip", integrating defined iPSC-derived neural networks into a 3D scaffold to reproduce a physiologically relevant brain cortical module that displays in vivo connectivity and activity.My involvement in the project has been to generate functional iPSC-derived microglia that will be added to the cortical architecture, along with astrocytes and interneurons. Techniques used to characterise microglia include immunocytochemsitry, q-RT-PCR, neuronal co-culture, cytokine analysis (ELISA, array-based assays) and analysis of ADP/ATP-evoked calcium transients.Alzheimer's/Neurodegeneration Translatable Disease ModelCollaboration with Sartorious (formerly Essen Bioscience). Project aims to use neuronal co-culture and tri-culture methods to investigate the function and relative contribution of microglia and astrocytes to the neuroinflammtory microenvironment of AD. Specifically, the research will make use of AD patient iPSC-derived neurons, astrocytes and microglia, and will showcase the applicability of Essen's Incucyte System for long-term monitoring of neuronal health and function in a disease model setting; the end goal being to generate a robust translatable model that could be used for studying cell-cell interactions or candidate drug screens. Production:Generation of iPSC-derived Neural Progenitor Cells (NPCs), Large-batch media productionDifferentiation of NPCs to cortical & dopaminergic neuronsGeneration of Alzheimer's Astrocyte iPSC-derived lineGeneration of iPSC-derived microglia and macrophagesOther duties:Lab purchasing coordinator; oversee lab purchasing and meet with suppliers Show less

Cambridge, United Kingdom

Lab Supervisor: Dr Nick Ktistakis (First 3 weeks)• Studied the process of autophagy, in particular the formation of the autophagosome • Used disruptive chemical treatments to interrogate pathway, followed by immunostaining of cells and visualisation on brightfield microscopes. Maintained a continuous epithelial cell line.Lab Supervisor: Dr Simon Walker (Last 5 weeks)• Investigated the potential of a novel microscopy technique known as Expansion Microscopy (ExM) for… Show more Lab Supervisor: Dr Nick Ktistakis (First 3 weeks)• Studied the process of autophagy, in particular the formation of the autophagosome • Used disruptive chemical treatments to interrogate pathway, followed by immunostaining of cells and visualisation on brightfield microscopes. Maintained a continuous epithelial cell line.Lab Supervisor: Dr Simon Walker (Last 5 weeks)• Investigated the potential of a novel microscopy technique known as Expansion Microscopy (ExM) for use at the institute, in which sub-resolution images can be obtained using conventional microscopes. • Involved substantial cell culture followed by various fixation methods and immunostaining. Imaged ExM-treated cells on brightfield, confocal and SIM microscopes. Used ImageJ and Nikon elements for image analysis. • Demonstrated proof-of-principle by capturing images of the same spindle fibres partaking in division before and after ExM procedure.• Independently produced a comprehensive, adapted ExM protocol optimised for employees at Babraham Show less

Huntingdon, Uk

• Carried out bacterial reverse mutation assays (Ames Tests) on various test compounds in order to quantify their potential genotoxicity. Involved bacterial culturing and handling of high hazard class substances up to and including level four.• Additionally, assisted in vivo studies in mice by formulating test compounds to exact concentration and pH, in accordance with company SOPs. Gained appreciation for the stringency applied in industry.• Took responsibility for the smooth running… Show more • Carried out bacterial reverse mutation assays (Ames Tests) on various test compounds in order to quantify their potential genotoxicity. Involved bacterial culturing and handling of high hazard class substances up to and including level four.• Additionally, assisted in vivo studies in mice by formulating test compounds to exact concentration and pH, in accordance with company SOPs. Gained appreciation for the stringency applied in industry.• Took responsibility for the smooth running of laboratory by taking stock checks, replenishing liquid nitrogen, media preparation, sterilization of equipment, and daily reporting of incubator, fridge, and freezer temperatures. Show less

Mbiolsci, 1:1

Lab Supervisor: Dr Stéphane Mesnage • Functionally characterised divisional and cell shape-determining proteins in the bacterium.

Bachelor Of Science - Bs, 2:1

Lab Supervisor: Dr Endre Kiss-Toth • Identified and quantified expression of candidate miRNAs regulating the expression of a protein known.