In this project, researchers are using nuclear magnetic resonance (NMR) spectroscopy to investigate unknown biological processes of the metabolism. This method is especially suitable for analysing the metabolome, for example the entire set of metabolic products of an organism or a cell. NMR spectroscopy can be used to determine structural information on molecules on a nanometre scale. In the »Targeted & Non-Targeted Metabolomics by Means of NMR Spectroscopy« project, NMR spectroscopy is used for both targeted and non-targeted metabolome analyses. The information obtained from targeted investigations into specified metabolite sets can, for example, contribute to the early diagnosis of disorders or to the monitoring of drug treatments. Non-targeted analyses are deployed in the investigation of biochemical networks and unknown metabolic pathways.
Metabolomic network models for incomplete reaction pathways
Along a metabolic pathway, enzymes normally trigger transformations successively. Incomplete specificity, instability or reactivity of some enzymes can, however, lead to incorrect chemical implementation. In a healthy metabolism, these unintended changes are compensated for or corrected by metabolic side-reactions. But if it is dysfunctional, there is the possibility that “non-canonical” metabolites come into being, for instance atypical variants of metabolites that can trigger diseases. To date, there has been very little research into metabolic side-reactions and there are hardly any possibilities to locate potential side-reactions in a reaction pathway in a targeted manner. Consequently, understanding these processes and identifying potential repair enzymes could provide great potential for the treatment of diseases.
In order to identify potential incomplete reaction pathways, researchers at ISAS are using NMR spectroscopy and mass spectrometry to construct network models of specific metabolites in certain sub-areas of the metabolic pathways. In further steps, they plan to identify potential underlying enzymatic reactions and enzymes of repair mechanisms.
Optimising NMR spectroscopy
Investigations using NMR spectroscopy are non-invasive and require only little sample preparation. In comparison to mass spectrometry, however, they feature a lower level of sensitivity. For this reason, the researchers are working to optimise the analytical method with regard to sensitivity. At the same time, they are pursuing the objective of also improving the sensitivity for samples of a limited mass and volume.
3D models of cells
A further focal point of the project is to develop new in vitro methods. Biological 3D printing makes it possible to create test models for specific biological issues in a targeted and flexible manner. The researchers are combining such models with microfluidic elements, labs-on-a-chip and with the deployment of cell models in the form of spheroids. This enables them to carry out analyses on systems that simulate, for example, the physiological conditions of a disease.
Results of an NMR spectroscopy analysis of 3D cell culture models. (a) shows light microscopic images of the model cells. Graphs b) and c) illustrate the intensities of proven metabolites in the cells. d) shows their relative radial distribution. Highlighted are: lactic acid (blue), glucose (grey) as well as the area in which the phosphorylcholine concentration exceeds half of its maximum value.
© ISAS / Roland Hergenröder
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Spectrochimica Acta A - Molecular and Biomolecular Spectroscopy, Vol. 307, 2024, P. 123594
Ababneh R, Telfah A, Al Bataineh QM, Tolstik E, Dierks J, Hergenröder R.
1H, 31P NMR, Raman and FTIR spectroscopies for investigating phosphoric acid dissociation to understand phosphate ion kinetics in body fluids.
https://doi.org/10.1016/j.saa.2023.123594
Journal of Alloys and Compounds, Vol. 971, 2024
Migdadi A, Al-Bataineh QM, Ahmad AA, Al-Khateeb H, Telfah A.
Titanium dioxide/reduced graphene oxide nanocomposites as effective photocatalytic for hazardous 4-nitrophenol
https://doi.org/10.1016/j.jallcom.2023.172794
Scientific reports, Vol. 13, 2023, P. 1-8
Al-Bataineh QM, Telfah A, Tavares CJ, Hergenröder R.
Surface plasmon coupling between wide-field SPR microscopy and gold nanoparticles
https://doi.org/10.1038/s41598-023-49583-3
Clinical Ophthalmology, Vol. 17, 2023, P. 3719-3728
Al-Dwairi R, Ahmad AA, Aleshawi A, Bani-Salameh AA, Aljarrah IA, Al-Bataineh QM, Al Beiruti S, Alshami AO, Rusen E, Toader G, Hergenröder R.
Silicone Oil Utilized in Pars Plana Vitrectomy for Patients with Advanced Proliferative Diabetic Retinopathy
https://doi.org/10.2147/OPTH.S447099
Journal of Molecular Structure, Vol. 1292, 2023, P. 136081
Telfah A, Shari'ah NA, Ababneh R, Bahti A, Al-Akhras M, Al-Hiari Y, Jum'h I, Abu-Dahab R, Telfah M, Bataineh QMA, Hergenröder R.
1H-NMR analysis of fluoroquinolone (pyridopyrrole quinoxaline, PPQ) conjugated to gold nanoparticles for synergistic anticancer drug design
https://doi.org/10.1016/j.molstruc.2023.136081
Journal of Inorganic and Organometallic Polymers and Materials, Vol. 33, No. 6, 2023, P. 1646-1656
Ababneh R, Smadi M, Bensiradj NEH, Al-Akhras MA, Al-Hiari Y, Jum'h I, Abu-Dahab R, Al Bataineh QM, Telfah A.
UV–Vis, FTIR and DFT Studies of the Fluoroquinolone [Pyrido Pyrolo Quinoxaline (PPQ)] Tethered to Gold Nanoparticles as a Novel Anticancer
https://doi.org/10.1007/s10904-023-02596-x
Physica B: Condensed Matter, Vol. 646, 2022
Telfah A, Al Bataineh Q, Mousa MS, Ababneh A, Sadiq D, Tavares CJ, Hergenröder R.
HR MAS NMR, dielectric impedance and XRD characterization of polyethylene oxide films for structural phase transitions
https://doi.org/10.1016/j.physb.2022.414353
Nature Communications, Vol. 13, No. 1, 2022, P. S68
Jeanclos E, Schlötzer J, Hadamek K, Yuan-Chen N, Al-Wahsh MI, Knitsch R, Fratz S, Yesiyurt-Gerhards D, Frankenbach T, Engelmann D, Keller A, Kaestner…
Glycolytic flux control by drugging phosphoglycolate phosphatase
https://doi.org/10.1038/s41467-022-34228-2
Journal of Applied Polymer Science, Vol. 139, No. 26, 2022, P. 1-11
Jum'h I, Telfah A, Mousa MS, Ahmad MJA, Tavares C, Hergenröder R.
XPS, UV–Vis, XRD, and PL spectroscopies for studying nickel nanoparticle positioning effect on nanocomposite film properties
https://doi.org/10.1002/app.52433
Computational and Structural Biotechnology Journal, Vol. 20, 2022, P. 2965-2977
Migdadi LYH, Telfah A, Hergenröder R, Wöhler C.
Novelty Detection for Metabolic Dynamics Established On Breast Cancer Tissue Using 2D NMR TOCSY Spectra
https://doi.org/10.1016/j.csbj.2022.05.050
Cancers, Vol. 14, No. 6, 2022
Alwahsh M, Knitsch R, Marchan R, Lambert J, Hoerner C, Zhang X, Schalke B, Lee D, Bulut E, Graeter T, Ott G, Kurz KS, Preissler G, Schölch S, Farhat…
Metabolic Profiling of Thymic Epithelial Tumors Hints to a Strong Warburg Effect, Glutaminolysis and Precarious Redox Homeostasis as Potential Therapeutic Targets
https://doi.org/10.3390/cancers14061564
Computational and Structural Biotechnology Journal, Vol. 19, 2021, P. 5047-5058
Migdadi LYH, Lambert J, Telfah A, Hergenröder R, Wöhler C.
Automated Metabolic Assignment: Semi-Supervised Learning in Metabolic Analysis Employing Two Dimensional Nuclear Magnetic Resonance (NMR)
https://doi.org/10.1016/j.csbj.2021.08.048