ORCID Profile
0000-0002-9955-6003
Current Organisation
University of Nottingham
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Publisher: American Society for Microbiology
Date: 26-12-2018
Abstract: Many yeasts undergo a morphological transition from yeast-to-hyphal growth in response to environmental conditions. We used forward and reverse genetic techniques to identify genes regulating this transition in Yarrowia lipolytica . We confirmed that the transcription factor Yl msn2 is required for the transition to hyphal growth and found that signaling by the histidine kinases Yl chk1 and Yl nik1 as well as the MAP kinases of the HOG pathway (Yl ssk2 , Yl pbs2 , and Yl hog1 ) regulates the transition to hyphal growth. These results suggest that Y. lipolytica transitions to hyphal growth in response to stress through multiple kinase pathways. Intriguingly, we found that a repetitive portion of the genome containing telomere-like and rDNA repeats may be involved in the transition to hyphal growth, suggesting a link between this region and the general stress response.
Publisher: Springer Science and Business Media LLC
Date: 15-03-2016
Publisher: Elsevier BV
Date: 09-2009
DOI: 10.1016/J.ACTBIO.2009.03.040
Abstract: The interactions of biomolecules and cells with solid interfaces play a pivotal role in a range of biomedical applications and have therefore been studied in great detail. An improved understanding of these interactions results in the ability to manipulate DNA, proteins and other biomolecules, as well as cells, spatially and temporally at surfaces with high precision. This in turn engenders the development of advanced devices, such as biosensors, bioelectronic components, smart biomaterials and microarrays. Spatial control can be achieved by the production of patterned surface chemistries using modern high-resolution patterning technologies based on lithography, microprinting or microfluidics, whilst temporal control is accessible through the application of switchable surface architectures. The combination of these two surface properties offers unprecedented control over the behaviour of biomolecules and cells at the solid-liquid interface. This review discusses the behaviour of biomolecules and cells at solid interfaces and highlights fundamental and applied research exploring patterned and switchable surfaces.
Publisher: SPIE
Date: 21-12-2008
DOI: 10.1117/12.759382
Publisher: Wiley
Date: 15-02-2023
Abstract: Biofilm formation is a major cause of hospital‐acquired infections. Research into biofilm‐resistant materials is therefore critical to reduce the frequency of these events. Polymer microarrays offer a high‐throughput approach to enable the efficient discovery of novel biofilm‐resistant polymers. Herein, bacterial attachment and surface chemistry are studied for a polymer microarray to improve the understanding of Pseudomonas aeruginosa biofilm formation on a erse set of polymeric surfaces. The relationships between time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS) data and biofilm formation are analyzed using linear multivariate analysis (partial least squares [PLS] regression) and a nonlinear self‐organizing map (SOM). The SOM models revealed several combinations of fragment ions that are positively or negatively associated with bacterial biofilm formation, which are not identified by PLS. With these insights, a second PLS model is calculated, in which interactions between key fragments (identified by the SOM) are explicitly considered. Inclusion of these terms improved the PLS model performance and shows that, without such terms, certain key fragment ions correlated with bacterial attachment may not be identified. The chemical insights provided by the combination of PLS regression and SOM will be useful for the design of materials that support negligible pathogen attachment.
Publisher: SPIE
Date: 16-02-2005
DOI: 10.1117/12.606789
Publisher: Springer Science and Business Media LLC
Date: 21-12-2020
DOI: 10.1038/S41467-020-20412-9
Abstract: A Correction to this paper has been published: 0.1038/s41467-020-20412-9.
Publisher: Elsevier BV
Date: 08-2015
DOI: 10.1016/J.CMET.2015.07.001
Abstract: The human gut microbiome is known to be associated with various human disorders, but a major challenge is to go beyond association studies and elucidate causalities. Mathematical modeling of the human gut microbiome at a genome scale is a useful tool to decipher microbe-microbe, diet-microbe and microbe-host interactions. Here, we describe the CASINO (Community And Systems-level INteractive Optimization) toolbox, a comprehensive computational platform for analysis of microbial communities through metabolic modeling. We first validated the toolbox by simulating and testing the performance of single bacteria and whole communities in vitro. Focusing on metabolic interactions between the diet, gut microbiota, and host metabolism, we demonstrated the predictive power of the toolbox in a diet-intervention study of 45 obese and overweight in iduals and validated our predictions by fecal and blood metabolomics data. Thus, modeling could quantitatively describe altered fecal and serum amino acid levels in response to diet intervention.
Publisher: Elsevier BV
Date: 2010
DOI: 10.1016/J.BIOMATERIALS.2009.09.056
Abstract: Many fundamental biological processes, including early embryo development, immune responses and the progression of pathogens, are mediated by gradients of biological molecules. Understanding these vital physiological processes requires the development of biomaterial platforms that can mimic them in-vitro. Such platforms include laboratory generated surface gradients of biological molecules. In this work, we report a method for the generation of surface gradients of two proteins. We used a surface grafting density gradient of polyethylene glycol (PEG) to control protein adsorption. In addition, we used protein size as a tool to control the position and the adsorbed amount of both proteins. To demonstrate our concept, we used fibrinogen as an ex le of a large protein and lysozyme as an ex le of a small protein. However, we speculate that the same strategy could be extended to any other pair of large and small proteins. We used X-ray photoelectron spectroscopy and sessile drop contact angle measurements to determine the chemical composition and wettability of the gradients. Protein adsorption was studied by surface plasmon resonance imaging.
Publisher: Humana Press
Date: 15-11-2011
DOI: 10.1007/978-1-61737-970-3_13
Abstract: DNA, protein and cell microarrays are increasingly used in a multitude of bioassays. All of these arrays require substrates that are suitable for the immobilisation and display of arrayed probe molecules whilst at the same time resisting non-specific interactions of biomolecules with the substrate in areas between printed spots. To meet these conflicting requirements, three different approaches have been developed, all of which were based on low-fouling, high-density poly(ethylene glycol) (PEG) background coatings. In the first approach, the coating was based on allylamine plasma polymerisation (ALAPP) and the subsequent high-density grafting of PEG, followed by the generation of a surface chemical pattern using laser ablation. In the second approach, a photoreactive polymer was printed on the same ALAPP-PEG background. The third approach was based on ALAPP deposition followed by the formation of a multifunctional layer by spin coating a PEG-based polymer that also displayed epoxy groups. The successful demonstration of DNA, protein and cell microarrays has been achieved on each of these coatings.
Publisher: Wiley
Date: 17-06-2013
Publisher: SPIE
Date: 27-12-2007
DOI: 10.1117/12.695595
Publisher: IEEE
Date: 06-2011
Publisher: SPIE
Date: 27-12-2007
DOI: 10.1117/12.695954
Publisher: American Chemical Society (ACS)
Date: 05-2009
DOI: 10.1021/LA900735N
Abstract: Polymer microarrays provide a high-throughput format in which to assess biointerfacial interactions. This endeavor greatly assists with the development of advanced biomaterials. In order to increase the scope of this platform technology, the development of analytical tools that are compatible with the microarray format and are capable of analyzing biomolecular interactions in high throughput is needed. Here, we show that surface plasmon resonance imaging (SPRi) is such a tool. SPRi enables spatially resolved, surface sensitive, label free, real-time analysis of multiple surface-biomolecular interactions in parallel. In order to demonstrate this, we first printed phenylazide-modified polymers onto a slide coated with a low fouling base polymer. UV irradiation of the slide resulted in the cross-linking of the printed polymer spots to the surface. SPRi was then employed to study the adsorption and desorption of bovine serum albumin, collagen, and fibronectin to these adhesive microarray spots. The spots were also incubated with an adherent cell line, enabling insight into the underlying mechanisms of cell attachment to the polymers studied. For the system analyzed here, electrostatic interactions were shown to dominate cell attachment.
Publisher: Springer Science and Business Media LLC
Date: 06-05-2020
Publisher: Elsevier BV
Date: 05-2008
Publisher: Springer Science and Business Media LLC
Date: 03-2020
Publisher: Cold Spring Harbor Laboratory
Date: 21-06-2018
DOI: 10.1101/350991
Abstract: Several studies have shown that neither the formal representation nor the functional requirements of genome-scale metabolic models (GEMs) are precisely defined. Without a consistent standard, comparability, reproducibility, and interoperability of models across groups and software tools cannot be guaranteed. Here, we present memote ( pencobra/memote ) an open-source software containing a community-maintained, standardized set of me tabolic mo del te sts. The tests cover a range of aspects from annotations to conceptual integrity and can be extended to include experimental datasets for automatic model validation. In addition to testing a model once, memote can be configured to do so automatically, i.e., while building a GEM. A comprehensive report displays the model’s performance parameters, which supports informed model development and facilitates error detection. Memote provides a measure for model quality that is consistent across reconstruction platforms and analysis software and simplifies collaboration within the community by establishing workflows for publicly hosted and version controlled models.
Publisher: Springer Science and Business Media LLC
Date: 19-10-2022
DOI: 10.1038/S41522-022-00348-2
Abstract: Recent studies have shown that probiotic supplementation has beneficial effects on bone metabolism. In a randomized controlled trial (RCT) we demonstrated that supplementation of Lactobacillus reuteri ATCC PTA 6475 reduced bone loss in older women with low bone mineral density. To investigate the mechanisms underlying the effect of L. reuteri ATCC PTA 6475 on bone metabolism, 20 women with the highest changes (good responders) and the lowest changes (poor responders) in tibia total volumetric BMD after one-year supplementation were selected from our previous RCT. In the current study we characterized the gut microbiome composition and function as well as serum metabolome in good responders and poor responders to the probiotic treatment as a secondary analysis. Although there were no significant differences in the microbial composition at high taxonomic levels, gene richness of the gut microbiota was significantly higher ( P 0.01 by the Wilcoxon rank-sum test) and inflammatory state was improved ( P 0.05 by the Wilcoxon signed-rank test) in the good responders at the end of the 12-month daily supplementation. Moreover, detrimental changes including the enrichment of E. coli (adjusted P 0.05 by DESeq2) and its biofilm formation ( P 0.05 by GSA) observed in the poor responders were alleviated in the good responders by the treatment. Our results indicate that L. reuteri ATCC PTA 6475 supplementation has the potential to prevent a deterioration of the gut microbiota and inflammatory status in elderly women with low bone mineral density, which might have beneficial effects on bone metabolism.
Publisher: EMBO
Date: 03-2017
Abstract: To elucidate the molecular mechanisms underlying non‐alcoholic fatty liver disease ( NAFLD ), we recruited 86 subjects with varying degrees of hepatic steatosis ( HS ). We obtained experimental data on lipoprotein fluxes and used these in idual measurements as personalized constraints of a hepatocyte genome‐scale metabolic model to investigate metabolic differences in liver, taking into account its interactions with other tissues. Our systems level analysis predicted an altered demand for NAD + and glutathione ( GSH ) in subjects with high HS . Our analysis and metabolomic measurements showed that plasma levels of glycine, serine, and associated metabolites are negatively correlated with HS , suggesting that these GSH metabolism precursors might be limiting. Quantification of the hepatic expression levels of the associated enzymes further pointed to altered de novo GSH synthesis. To assess the effect of GSH and NAD + repletion on the development of NAFLD , we added precursors for GSH and NAD + biosynthesis to the Western diet and demonstrated that supplementation prevents HS in mice. In a proof‐of‐concept human study, we found improved liver function and decreased HS after supplementation with serine (a precursor to glycine) and hereby propose a strategy for NAFLD treatment.
Publisher: Springer Science and Business Media LLC
Date: 19-03-2020
DOI: 10.1038/S41587-020-0477-4
Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Publisher: Elsevier BV
Date: 10-2002
Publisher: Springer Science and Business Media LLC
Date: 02-2022
DOI: 10.1038/S41591-022-01688-4
Abstract: Previous microbiome and metabolome analyses exploring non-communicable diseases have paid scant attention to major confounders of study outcomes, such as common, pre-morbid and co-morbid conditions, or polypharmacy. Here, in the context of ischemic heart disease (IHD), we used a study design that recapitulates disease initiation, escalation and response to treatment over time, mirroring a longitudinal study that would otherwise be difficult to perform given the protracted nature of IHD pathogenesis. We recruited 1,241 middle-aged Europeans, including healthy in iduals, in iduals with dysmetabolic morbidities (obesity and type 2 diabetes) but lacking overt IHD diagnosis and in iduals with IHD at three distinct clinical stages—acute coronary syndrome, chronic IHD and IHD with heart failure—and characterized their phenome, gut metagenome and serum and urine metabolome. We found that about 75% of microbiome and metabolome features that distinguish in iduals with IHD from healthy in iduals after adjustment for effects of medication and lifestyle are present in in iduals exhibiting dysmetabolism, suggesting that major alterations of the gut microbiome and metabolome might begin long before clinical onset of IHD. We further categorized microbiome and metabolome signatures related to prodromal dysmetabolism, specific to IHD in general or to each of its three subtypes or related to escalation or de-escalation of IHD. Discriminant analysis based on specific IHD microbiome and metabolome features could better differentiate in iduals with IHD from healthy in iduals or metabolically matched in iduals as compared to the conventional risk markers, pointing to a pathophysiological relevance of these features.
Publisher: IEEE
Date: 06-2010
Publisher: Elsevier BV
Date: 10-2006
DOI: 10.1016/J.TIBTECH.2006.08.001
Abstract: Many biological events, such as cellular communication, antigen recognition, tissue repair and DNA linear transfer, are intimately associated with biomolecule interactions at the solid-liquid interface. To facilitate the study and use of these biological events for biodevice and biomaterial applications, a sound understanding of how biomolecules behave at interfaces and a concomitant ability to manipulate biomolecules spatially and temporally at surfaces is required. This is particularly true for cell microarray applications, where a range of biological processes must be duly controlled to maximize the efficiency and throughput of these devices. Of particular interest are transfected-cell microarrays (TCMs), which significantly widen the scope of microarray genomic analysis by enabling the high-throughput analysis of gene function within living cells. This article reviews this current research focus, discussing fundamental and applied research into the spatial and temporal surface manipulation of DNA, proteins and other biomolecules and the implications of this work for TCMs.
Publisher: Elsevier BV
Date: 05-2006
DOI: 10.1016/J.BIOS.2005.10.008
Abstract: The manipulation of biomolecules at solid/liquid interfaces is important for the enhanced performance of a number of biomedical devices, including biochips. This study focuses on the spatial control of surface interactions of DNA as well as the electro-stimulated adsorption and desorption of DNA by appropriate surface modification of highly doped p-type silicon. Surface modification by plasma polymerisation of allylamine resulted in a surface that supported DNA adsorption and sustained cell attachment. Subsequent high-density grafting of poly(ethylene oxide) formed a low fouling layer resistant to biomolecule adsorption and cell attachment. Spatially controlled excimer laser ablation of the surface produced patterns of re-exposed plasma polymer with high-resolution. On patterned surfaces, preferential electro-stimulated adsorption of DNA to the allylamine plasma polymer surface and subsequent desorption by the application of a negative bias was observed. Furthermore, the concept presented here was investigated for use in transfection chips. Cell culture experiments with human embryonic kidney cells, using the expression of green fluorescent protein as a reporter, demonstrated efficient and controlled transfection of cells. Electro-stimulated desorption of DNA was shown to yield significantly enhanced solid phase transfection efficiencies to values of up to 30%. The ability to spatially control DNA adsorption combined with the ability to control the binding and release of DNA by application of a controlled voltage enables an advanced level of control over DNA bioactivity on solid substrates and lends itself to biochip applications.
Publisher: American Chemical Society (ACS)
Date: 09-03-2009
DOI: 10.1021/BM801217N
Abstract: The fabrication and characterization of chemical patterns using a technique that can be readily integrated with methods currently used for the formation of microarrays is presented. A high density poly(ethylene glycol) coating was deposited on glass slides as a background exhibiting low cell attachment properties. Phenylazide modified polymers were then printed on this background. UV irradiation of these polymer arrays resulted in the cross-linking of the polymer spots and their covalent attachment to the surface. Cell attachment was shown to follow the resultant surface chemistry pattern. Furthermore, the use of a robotic contact printer enabled the facile deposition of DNA microarrays on top of and aligned with the polymer microarrays. A transfected cell microarray was generated in this way, demonstrating not only the ability of this platform to limit cell attachment to specific regions, but the suitability for chip-based functional genomics, in particular, and high density cell assays in general.
Publisher: Springer Science and Business Media LLC
Date: 18-11-2020
DOI: 10.1038/S41467-020-19589-W
Abstract: Microbiota-host-diet interactions contribute to the development of metabolic diseases. Imidazole propionate is a novel microbially produced metabolite from histidine, which impairs glucose metabolism. Here, we show that subjects with prediabetes and diabetes in the MetaCardis cohort from three European countries have elevated serum imidazole propionate levels. Furthermore, imidazole propionate levels were increased in subjects with low bacterial gene richness and Bacteroides 2 enterotype, which have previously been associated with obesity. The Bacteroides 2 enterotype was also associated with increased abundance of the genes involved in imidazole propionate biosynthesis from dietary histidine. Since patients and controls did not differ in their histidine dietary intake, the elevated levels of imidazole propionate in type 2 diabetes likely reflects altered microbial metabolism of histidine, rather than histidine intake per se. Thus the microbiota may contribute to type 2 diabetes by generating imidazole propionate that can modulate host inflammation and metabolism.
Publisher: American Chemical Society (ACS)
Date: 23-10-2018
Abstract: The identification of biomaterials that modulate cell responses is a crucial task for tissue engineering and cell therapy. The identification of novel materials is complicated by the immense number of synthesizable polymers and the time required for testing each material experimentally. In the current study, polymeric biomaterial-cell interactions were assessed rapidly using a microarray format. The attachment, proliferation, and differentiation of human dental pulp stem cells (hDPSCs) were investigated on 141 homopolymers and 400 erse copolymers. The copolymer of isooctyl acrylate and 2-(methacryloyloxy)ethyl acetoacetate achieved the highest attachment and proliferation of hDPSC, whereas high cell attachment and differentiation of hDPSC were observed on the copolymer of isooctyl acrylate and trimethylolpropane ethoxylate triacrylate. Computational models were generated, relating polymer properties to cellular responses. These models could accurately predict cell behavior for up to 95% of materials within a test set. The models identified several functional groups as being important for supporting specific cell responses. In particular, oxygen-containing chemical moieties, including fragments from the acrylate/acrylamide backbone of the polymers, promoted cell attachment. Small hydrocarbon fragments originating from polymer pendant groups promoted cell proliferation and differentiation. These computational models constitute a key tool to direct the discovery of novel materials within the enormous chemical space available to researchers.
Publisher: Cold Spring Harbor Laboratory
Date: 23-03-2023
DOI: 10.1101/2023.03.21.512712
Abstract: The field of metabolic modelling at the genomescale continues to grow with more models being created and curated. This comes with an increasing demand for adopting common principles regarding transparency and versioning, in addition to standardisation efforts regarding file formats, annotation and testing. Here, we present a standardised template for git-based and GitHub-hosted genome-scale metabolic models (GEMs) supporting both new models and curated ones, following FAIR principles (findability, accessibility, interoperability, and reusability), and incorporating bestpractices. standard-GEM facilitates the reuse of GEMs across web services and platforms in the metabolic modelling field and enables automatic validation of GEMs. The use of this template for new models, and its adoption for existing ones, paves the way for increasing model quality, openness, and accessibility with minimal effort. standard-GEM is available from github.com/MetabolicAtlas/standard-GEM under the conditions of the CC BY 4.0 licence along with additional supporting material.
Publisher: IOP Publishing
Date: 30-10-2009
DOI: 10.1088/1758-5082/1/4/045003
Abstract: The spatial control over biomolecule- and cell-surface interactions is of great interest to a broad range of biomedical applications, including sensors, implantable devices and cell microarrays. Microarrays in particular require precise spatial control and the formation of patterns with microscale features. Here, we have developed an approach specifically designed for transfected cell microarray (TCM) applications that allows microscale spatial control over the location of both DNA and cells on highly doped p-type silicon substrates. This was achieved by surface modification, involving plasma polymerization of allylamine, grafting of poly(ethylene glycol) and subsequent excimer laser ablation. DNA could be delivered in a spatially defined manner using ink-jet printing. In addition, electroporation was investigated as an approach to transfect attached cells with adsorbed DNA and good transfection efficiencies of approximately 20% were observed. The ability of the microstructured surfaces to spatially direct both DNA adsorption and cell attachment was demonstrated in a functional TCM, making this system an exciting platform for chip-based functional genomics.
Publisher: American Chemical Society (ACS)
Date: 04-2020
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Jens Nielsen.