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Abcam plc

Country: United Kingdom
6 Projects, page 1 of 2
  • Funder: UKRI Project Code: BB/I015914/3
    Funder Contribution: 68,045 GBP

    Over the past ten years or so, the Teichmann group and others have shown that the ensemble of transcriptional regulatory interactions in a cell or organism forms a network, which can be described and analysed using bioinformatics, graph theory and mathematical modelling to reveal profound new insights (e.g. Teichmann & Babu, Nature Genet., 2004; Luscombe et al., Nature, 2004). Transcriptional regulatory networks control development and differentiation (e.g. Soneji et al., Ann. N.Y. Acad. Sci., 2007), and here we propose to study the differentiation of T helper cell types of the immune system. The T helper (Th) cell system, one terminal branch of haematopoiesis (Reiner, Cell, 2007), is an experimentally amenable model of differentiation with the added advantage that the various Th cell types can be obtained in large amounts as homogeneous populations. It is also of fundamental importance to human health. The Th cell system regulates immune responses, and impairment of the T helper cell compartment leads to dramatic immune deficiency as seen in late-phase HIV infections (7). Misbalanced differentiation from naïve T helper cells to one of the currently known subtypes, Th1, 2 and 17 and iTregs, is causally involved in diseases like autoimmunity and allergy (Reiner, Cell, 2007). The whole Th differentiation process from naïve Th cells to the three mature subtypes (Th1, 2 and 17) as well as iTregs, can be followed in large numbers of primary cells, and can be accurately simulated in vitro from primary T cells (Reiner, Cell, 2007). The signalling within and between cells in tissues that takes place in most animal developmental and differentiation process is limited in Th differentiation, as the cells are practically not matrix-associated, and their inter-cell interactions are well characterised and can be simulated in vitro (Reiner, Cell, 2007). Therefore, the Th system provides an ideal model to study the transcriptional changes ensuing upon differentiation. There are several fundamental questions about the role of transcriptional regulation in differentiation that can be addressed in this system. First, only a handful of transcription factors (TFs) have been identified for each subtype. Therefore, we propose to identify new candidate transcription factors for each Th subtype by deep sequencing (RNA-seq) of each subtype in a timecourse, and subsequent bioinformatics analysis of the data. This will provide insight into the complexity of the network underlying differentiation into each subtype. Secondly, we will look for binding sites of these transcription factors using both computational screens and Chromatin Immunoprecipitation followed by sequencing (ChIP-seq). It will be crucial to have ChIP-grade antibodies for these transcription factors. We know already from published microarray data that there are will be a number of transcription factors in Th cells that are poorly characterised, with either no antibody or no ChIP-grade antibody commercially available. This is where antibody development is essential, and where Abcam will be instrumental in driving the project forward. These ChIP-seq and computational analyses will shed light on the molecules involved and the topology of their interactions. Thirdly, by superimposing ChIP-seq data of histone modifications on these transcriptional regulatory interactions, we will evaluate the role of chromatin-level regulation in the differentiation process.

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  • Funder: UKRI Project Code: BB/I01604X/1
    Funder Contribution: 91,932 GBP

    Prior work by the Millner laboratory, principally arising from EC Framework 6 Project ELISHA, led to the development of a new electrochemical immunosensor platform. ELISHA immunosensors comprise immobilised antibodies on the surface of a transducer and can be interrogated by AC impedance or electrical pulse decay after binding the analyte to be interrogated. The sensors are truly reagentless and measurement is simply 'incubate and read' with quantification of the analyte being carried out against a calibration curve. Background signal is typically much less than 10-15% of specific signal and can be accounted by two main approaches; tuning of the sensor surface chemistry for the analyte and matrix in which it occurs, and subtraction of a 'control' electrode signal that bears a non-specific antibody. To date we have demonstrated the ELISHA principle for >30 analytes, ranging from heavy metal ions, through small molecules like pesticides and antibiotics, macromolecules such as various protein markers of disease, and up to viruses and bacteria. ELISHA immunosensors function in 'real' fluids such as milk, serum and blood, urine and saliva with no prior processing. We are now at a stage where ELISHA commercialisation is being actively pursued and the challenge is to understand how best to fabricate immunosensor chips to acceptable batch reproducibility. In addition we wish to develop multi-analyte 'mini-array'chips where a panel of up to 10-12 analytes can be measured simultaneously within a sample. Discussion with both medical and veterinary companies and with the biotech industry servicing life science R & D indicates this to be a major requirement. Against this background Abcam Ltd, globally one of the major suppliers of antibodies for R & D; wish to collaborate with us in developing such a multi-analyte platform which for them will represent a future product portfolio. For the academic partner, the alliance would give access to Abcam's very large product portfolio and expertise in producing and handling all types of antibodies. The project strategy will be to examine ELISHA biosensor fabrication and interrogation at four key points. These are electrode (transducer) design, optimisation of transducer composition and nanostructure, optimisation of surface chemistry for antibody coupling from the several approaches available to us, and choice of best interrogation strategy. To accomplish these aims we will work with panels of antibodies, where the analytes are also readily available. Electrodes will be fabricated by both screen printing and inkjet procedures and several multi-electrode layouts will be compared. Then a range of conducting polymeric surfaces will be compared, bearing appropriate pendant chemical groups (amine, hydroxyl, and thiol) to permit gentle chemical coupling of antibodies to the transducer surface. Direct coupling and affinity mediated coupling (avidin/biotin, complementary oliognucleotide pairs), and non-specific versus oriented antibody immobilisation, will be compared. Finally, low frequency AC impedance interrogation protocols will be compared with fast pulsed electrochemical approaches we have developed; if the fast pulsed methodology gives reproducible measurements this would represent a step improvement in biosensor interrogation. During the project we will focus on antibody/analyte sets for which is an analytical requirement is known by Abcam to exist within the R& D community (e.g. cytokines, second messengers, protein and peptide neurotransmitters). We also have expertise in place to drive onward development of any successful findings emerging from this project. ELISHA Systems Ltd, a spin-out from project ELISHA and Uniscan Instruments Ltd, a partner in the ELISHA project, already have IP in place and a prototype ELISHA chip reader respectively which could be further developed to produce a simple handheld chip reader for the generic multi-analyte immunosensors we hope to develop.

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  • Funder: UKRI Project Code: BB/I015914/1
    Funder Contribution: 91,932 GBP

    Over the past ten years or so, the Teichmann group and others have shown that the ensemble of transcriptional regulatory interactions in a cell or organism forms a network, which can be described and analysed using bioinformatics, graph theory and mathematical modelling to reveal profound new insights (e.g. Teichmann & Babu, Nature Genet., 2004; Luscombe et al., Nature, 2004). Transcriptional regulatory networks control development and differentiation (e.g. Soneji et al., Ann. N.Y. Acad. Sci., 2007), and here we propose to study the differentiation of T helper cell types of the immune system. The T helper (Th) cell system, one terminal branch of haematopoiesis (Reiner, Cell, 2007), is an experimentally amenable model of differentiation with the added advantage that the various Th cell types can be obtained in large amounts as homogeneous populations. It is also of fundamental importance to human health. The Th cell system regulates immune responses, and impairment of the T helper cell compartment leads to dramatic immune deficiency as seen in late-phase HIV infections (7). Misbalanced differentiation from naïve T helper cells to one of the currently known subtypes, Th1, 2 and 17 and iTregs, is causally involved in diseases like autoimmunity and allergy (Reiner, Cell, 2007). The whole Th differentiation process from naïve Th cells to the three mature subtypes (Th1, 2 and 17) as well as iTregs, can be followed in large numbers of primary cells, and can be accurately simulated in vitro from primary T cells (Reiner, Cell, 2007). The signalling within and between cells in tissues that takes place in most animal developmental and differentiation process is limited in Th differentiation, as the cells are practically not matrix-associated, and their inter-cell interactions are well characterised and can be simulated in vitro (Reiner, Cell, 2007). Therefore, the Th system provides an ideal model to study the transcriptional changes ensuing upon differentiation. There are several fundamental questions about the role of transcriptional regulation in differentiation that can be addressed in this system. First, only a handful of transcription factors (TFs) have been identified for each subtype. Therefore, we propose to identify new candidate transcription factors for each Th subtype by deep sequencing (RNA-seq) of each subtype in a timecourse, and subsequent bioinformatics analysis of the data. This will provide insight into the complexity of the network underlying differentiation into each subtype. Secondly, we will look for binding sites of these transcription factors using both computational screens and Chromatin Immunoprecipitation followed by sequencing (ChIP-seq). It will be crucial to have ChIP-grade antibodies for these transcription factors. We know already from published microarray data that there are will be a number of transcription factors in Th cells that are poorly characterised, with either no antibody or no ChIP-grade antibody commercially available. This is where antibody development is essential, and where Abcam will be instrumental in driving the project forward. These ChIP-seq and computational analyses will shed light on the molecules involved and the topology of their interactions. Thirdly, by superimposing ChIP-seq data of histone modifications on these transcriptional regulatory interactions, we will evaluate the role of chromatin-level regulation in the differentiation process.

    more_vert
  • Funder: UKRI Project Code: BB/I015914/2
    Funder Contribution: 82,407 GBP

    Over the past ten years or so, the Teichmann group and others have shown that the ensemble of transcriptional regulatory interactions in a cell or organism forms a network, which can be described and analysed using bioinformatics, graph theory and mathematical modelling to reveal profound new insights (e.g. Teichmann & Babu, Nature Genet., 2004; Luscombe et al., Nature, 2004). Transcriptional regulatory networks control development and differentiation (e.g. Soneji et al., Ann. N.Y. Acad. Sci., 2007), and here we propose to study the differentiation of T helper cell types of the immune system. The T helper (Th) cell system, one terminal branch of haematopoiesis (Reiner, Cell, 2007), is an experimentally amenable model of differentiation with the added advantage that the various Th cell types can be obtained in large amounts as homogeneous populations. It is also of fundamental importance to human health. The Th cell system regulates immune responses, and impairment of the T helper cell compartment leads to dramatic immune deficiency as seen in late-phase HIV infections (7). Misbalanced differentiation from naïve T helper cells to one of the currently known subtypes, Th1, 2 and 17 and iTregs, is causally involved in diseases like autoimmunity and allergy (Reiner, Cell, 2007). The whole Th differentiation process from naïve Th cells to the three mature subtypes (Th1, 2 and 17) as well as iTregs, can be followed in large numbers of primary cells, and can be accurately simulated in vitro from primary T cells (Reiner, Cell, 2007). The signalling within and between cells in tissues that takes place in most animal developmental and differentiation process is limited in Th differentiation, as the cells are practically not matrix-associated, and their inter-cell interactions are well characterised and can be simulated in vitro (Reiner, Cell, 2007). Therefore, the Th system provides an ideal model to study the transcriptional changes ensuing upon differentiation. There are several fundamental questions about the role of transcriptional regulation in differentiation that can be addressed in this system. First, only a handful of transcription factors (TFs) have been identified for each subtype. Therefore, we propose to identify new candidate transcription factors for each Th subtype by deep sequencing (RNA-seq) of each subtype in a timecourse, and subsequent bioinformatics analysis of the data. This will provide insight into the complexity of the network underlying differentiation into each subtype. Secondly, we will look for binding sites of these transcription factors using both computational screens and Chromatin Immunoprecipitation followed by sequencing (ChIP-seq). It will be crucial to have ChIP-grade antibodies for these transcription factors. We know already from published microarray data that there are will be a number of transcription factors in Th cells that are poorly characterised, with either no antibody or no ChIP-grade antibody commercially available. This is where antibody development is essential, and where Abcam will be instrumental in driving the project forward. These ChIP-seq and computational analyses will shed light on the molecules involved and the topology of their interactions. Thirdly, by superimposing ChIP-seq data of histone modifications on these transcriptional regulatory interactions, we will evaluate the role of chromatin-level regulation in the differentiation process.

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  • Funder: UKRI Project Code: ST/K002082/1
    Funder Contribution: 48,963 GBP

    Early diagnosis and treatment of cancer prior to metastasis has a significant impact on patient survival. This project will demonstrate novel luminescent optical imaging agents that could lead to safe, extremely accurate, non-invasive and affordable early diagnostics of cancers which are difficult to access non-invasively due to limited light penetration through tissues such as the alimentary tract. Our RCaH-MGU-Bath collaboration will utilize our joint expertise in chemistry, biophysics and bioimaging in vitro and in vivo to exploit unique nanomaterials. We will attach tumour targeting peptides and commercial antibodies for cancer cell markers (Abcam) to near-infrared emitting luminescent nanoparticles (synthesised at Bath and also those available via the project partner, Intrinsiq Materials Ltd). These conjugates will be investigated at Bath and at the RCaH for selective delivery to cancer cells, uptake, toxicity, in vitro and in vivo optical imaging using multiphoton fluorescence imaging, lifetime imaging and in vivo bioluminescence. Jointly with our project partners (Abcam Plc, Intrinsiq Materials Ltd and Nikon Bioimaging UK) we will develop a design and testing integrated technology for the nanoparticles to attract investment for early cancer diagnostic by novel imaging agents. This will open up an opportunity to validate this technology which will allow us to tap into the $3.3 billion medical diagnostics market upon completion of the project. A deeper understanding of interactions between nanoparticles and cancer cells and a full investigation into their chemical biology will also emerge as a result, which is crucial to the delivery of new, marketable, diagnostic tools. The state-of-the-art relies on the use of organic molecules as imaging agents that normally suffer from short emission lifetime and poor photostability or use of quantum dots, which are of high cost and biologically toxic. We will carry out the first benchmark study of toxicity, in vitro targeting of cancer cells and in vivo bioluminescence imaging. This project will deliver the imaging probe as a result of the close collaboration between synthetic chemists, imaging technologist, chemical biologists and cell biologists. We will demonstrate that near-IR emitting nanoparticles (NPs), functionalized with peptides and antibodies can be applied to the medical diagnostics market by overcoming disadvantages of existing fluorophores e.g. quantum dots (cost and toxicity) and organic fluorophores (short life span). This project can pave the way to address the unmet clinical need for future endoscopes operating in the NIR regime and adapted to bypass tissue autofluorescence. It can also lead to the development of new medical diagnostic tools in future developments with colleagues in the Biosensing Network at Bath and with the clinical collaborators from the Cancer Research at Bath network.

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