Christian Johannessen

Research Christian Johannessen

Research team

Expertise

Structural analysis of biomacromolecules by a combination of experimental chiroptical spectroscopic techniques (Raman optical activity, vibrational and electronic circular dichroism) and molecular modelling (molecular dynamics and quantum mechanical calculations). Method and instrument development.

Steady-state and time-resolved fluorescence spectroscopy (FLUORATE). 01/06/2022 - 31/05/2024

Abstract

Optical materials are ubiquitous in present society. From the building blocks of displays and LEDs, to fibre optic communication for ultrafast internet, (plasmonic) nanostructures for photocatalysis, bulk heterojunctions for photovoltaics, probes for imaging, sensing and revealing reaction mechanisms in chemistry and catalysis and various nanostructures for nanophotonics applications. The in-depth knowledge on the nature and dynamics of the surface and bulk properties of these materials, such as the fate of electrons and holes that arise after optical excitation requires dedicated spectroscopic techniques that can reveal both steady-state and time-resolved properties of such materials. Fluorescence spectroscopy is one of the most versatile and sensitive techniques that can provide such information. Modern detectors are able to detect single photons that are emitted at time scales ranging from several picoseconds to seconds, and with energies spanning the entire UV, visible and NIR optical range. The system applied for is a versatile steady-state and time-resolved fluorescence spectrometer, that is highly modular and when combined with the already available infrastructure, provides a unique configuration allowing a wide range of experiments that provide information on a.o. ultrafast processes at picosecond timescales, delayed fluorescence from for example triplet states and with a sensitivity over a very broad wavelength range (200 – 1700nm) and accessibility to both ensemble and single-molecule detection from solutions, powders, nanoparticles, films and devices. The infrastructure will be applied in very different research fields, from photocatalysis to excitonic properties of nanomaterials, and from chemical reaction kinetics to photovoltaic and LED applications, which is also confirmed by the very diverse research topics of the 5 involved research teams.

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Project type(s)

  • Research Project

Replacement of an existing Vibrational Circular Dichroism spectrometer. 01/01/2020 - 31/12/2021

Abstract

In 2003, an FWO project of W. Herrebout (Molecular Spectroscopy) and P. Bultinck (Ghent Quantum Chemistry Group, Ghent University) led to the purchase of a Bruker PMA37 module. The module was connected to an existing Bruker IFS66v FTIR spectrometer purchased in 1998. Apart from standard infrared spectra, the combination of an FTIR research spectrometer and a dedicated PMA37 polarisation accessory allowed to obtain vibrational circular dichroism (VCD) spectra, in which small differences in absorbance of left and right circularly polarised IR light by a chiral sample are detected. Continuous maintenance of the FTIR instrument, including updates of the dedicated PC in 2003 and 2011, and tedious re-alignment of the optical bench of the VCD accessory by the local PI at regular intervals, allowed the set-up to be used for research and fee-for-service activities on an almost continuous basis up to 2019. In June 2019, electronic problems with the acquisition card controling the optical bench of the Bruker IFS66v FTIR spectrometer was detected. Discussions with E. Huys, FTIR service engineer at Bruker Belgium, and the engineers responsible at the Bruker Optics headquarters in Ettlingen (Germany) finally led to the conclusion that due to the out-dated electronics used in the FTIR spectrometer, the current set-up could no longer be supported. Moreover, taking into account further developments of the VCD module, including amongst others, the use of a more recent piezoelectric modulator working at a significantly higher frequency (42 kHz in the more recent PMA50 vs. 37 kHz in the older PMA37), and the use of more developed acquisition cards and electronics replacing the existing lock-in amplifier currently used in the PMA37 module, the existing module unfortunately could not be coupled to the Vertex or Inventio-R FTIR spectrometers currently supplied by Bruker Optics. To allow the research lines involving vibrational circular dichroism to be further developed, and to ensure the existing local and international fee-for-service activities employing VCD, in the current proposal, financial support allowing the replacement of the current set-up is requested.

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  • Research Project

Stimulating NILS (Nanoelectromechanical Instruments for Life Sciences). 01/12/2019 - 30/11/2021

Abstract

The following is the abstract of our FET application: We want to introduce radically new instruments based on nanoelectromechanical systems (NEMS) for a qualitative and quantitative improvement of key methods in life sciences. The foundational concept justifying this vision is the incomparable infrared (IR) detection sensitivity that NEMS can achieve. In a recent breakthrough, we have introduced a method to optimize NEMS detectors to reach single-molecule sensitivity at room temperature with unprecedented signal-to-noise ratio. The obtained sensitivity of a few femtowatts per square root hertz not only corresponds to an improvement of three orders of magnitude over existing similar NEMS technology, but also over comparable state-of-the-art room temperature infrared detectors. The main objective of this project is to apply this unprecedented sensitivity to: 1. improve minimal sample mass necessary for IR protein quantification from nanograms to femtograms, 2. improve biomolecule secondary structure analysis and chiral configuration determination via IR vibrational circular dichroism by reducing the time required for an analysis from hours to minutes, 3. enable IR identification of single cancer cells and single bacteria for the first time, and 4. enable IR analysis of signaling metabolites of single biofilm-forming bacteria for the first time. Our NEMS IR spectroscopic instruments will set new analytic paradigms in key areas in life sciences such as proteomics, bacteriology, pharmacology, cell biology, microbiology, and oncology. In these fields, the new set of instruments will drastically speed up drug discovery, cancerous cell screening, effective antibiotic treatment, and help to understand and prohibit the formation of dangerous biofilms. The entire basis of the consortium that has been put together for this FET application (for which we will resubmit an improved application) is instrument development. In the MolSpec group, building instruments is a fairly recent addition to our research portfolio, starting with me joining the group in 2013. Thus, it has been a privilege to have our expertise recognized by my colleagues in the consortium and I would like to boost this international visibility even further. Hence, the SEP project I propose will invest further into instrument development in IR and Raman based chiroptical spectroscopy, investigating and building new and improved laser based light sources and detectors/spectrographs, in order to improve measuring speed and detection limits of the techniques already employed in our group. In addition to directly linking with the research proposed in the FET application, building proof-of-concept instruments for bench marking against the current commercial technology would strengthen our efforts in applying for further funding from other sources, as well as the ERC, and should make the group a desirable member in other international consortia.

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  • Research Project

Exploring the three-dimensional structure of antimicrobial peptides through optical activity spectroscopy. 01/10/2019 - 30/09/2023

Abstract

The rise in antimicrobial resistance (AMR) may lead to international unrest, as it threatens the global society and economics of the future due to the lack of new antibiotics. Therefore, pharmaceutical companies search for novel antibiotics that will neutralize the threat of bacteria exhibiting AMR. Presently, the target of this search is increasingly focused on the promising class of nature-discovered antimicrobial peptides (AMPs). In order to exploit the naturally occurring AMPs in the development of new resistance-free human antibiotics, the activity of these must be related to their mechanism of action. In order to study the three-dimensional structure of AMPs in solution -which provides crucial information regarding the mechanism of action-, chemists traditionally use nuclear magnetic resonance (NMR) spectroscopy. However, when NMR is employed in combination with optical spectroscopic techniques, a more detailed structural picture of the compound becomes available, essential for rational drug design of new antibiotics. This research project aims to combine Raman optical activity, vibrational circular dichroism and electronic circular dichroism with NMR data available in the literature to study AMPs. The AMPs vancomycin, ramoplanin and daptomycin will be subjected to a full structural study, both alone in solution and in interaction with their biological targets within the bacterial cell. The main focus lays on the relationship between the observed spectral features and three-dimensional structural aspects of the compounds. Finally, this will allow for the development of a methodology applicable onto a broad range of AMPs that are of interest in the pharmaceutical world.

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  • Research Project

Studying the structure-activity relationship in artemisinin-transferrin adducts by means of Raman optical activity. 01/10/2019 - 30/09/2021

Abstract

Cancer has become an ever increasing risk in our aging Western world. As a consequence of a rise in diagnosed cancer cases, in combination with the limitations and side effects caused by conventional cancer treatments, new cancer therapies with high efficiency and limited side effects are much sought after. Artemisinin, a drug already used in malaria treatment, is showing great potential as a candidate for such next generation cancer treatment. Unfortunately, due to the complexity of the current drug assembly, as artemisinin is delivered to the cancer cells bound to the iron transporting protein transferrin, efforts in clinical development of the drug is slow. In this project, a protocol for the detailed structural analysis of artemisinin-transferrin complexes is proposed. By studying the solution phase structure of the drug, using state-of-the-art chiroptical spectroscopic techniques combined with cutting-edge computational chemistry, and correlating these findings with anticancer activity studies, it is hoped that the process of developing artemisinin into a viable anticancer drug will be stream lined before the costly (both with respect to money and time) clinical trials. Therefore, it is also envisioned that the protocol will define precedence for other pre-clinical protein drug studies.

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  • Research Project

Studying the structure-activity relationship in artemisinin-transferrin adducts by means of Raman optical activity 01/10/2017 - 30/09/2019

Abstract

Cancer has become an ever increasing risk in our aging Western world. As a consequence of a rise in diagnosed cancer cases, in combination with the limitations and side effects caused by conventional cancer treatments, new cancer therapies with high efficiency and limited side effects are much sought after. Artemisinin, a drug already used in malaria treatment, is showing great potential as a candidate for such next generation cancer treatment. Unfortunately, due to the complexity of the current drug assembly, as artemisinin is delivered to the cancer cells bound to the iron transporting protein transferrin, efforts in clinical development of the drug is slow. In this project, a protocol for the detailed structural analysis of artemisinin-transferrin complexes is proposed. By studying the solution phase structure of the drug, using state-of-the-art chiroptical spectroscopic techniques combined with cutting-edge computational chemistry, and correlating these findings with anticancer activity studies, it is hoped that the process of developing artemisinin into a viable anticancer drug will be stream lined before the costly (both with respect to money and time) clinical trials. Therefore, it is also envisioned that the protocol will define precedence for other pre-clinical protein drug studies.

Researcher(s)

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Project type(s)

  • Research Project

Studying structure-function relationships in transferrin-artemisinin adducts by means of Raman optical activity. 01/10/2016 - 30/09/2017

Abstract

Cancer has become an ever increasing risk in our aging Western world. As a consequence of a rise in diagnosed cancer cases, in combination with the limitations and side effects caused by conventional cancer treatments, new canter therapies with high efficiency and limited side effects are much sought after. Artemisinin, a drug already used in malaria treatment, is showing great potential as a candidate for such next generation cancer treatment. Unfortunately, due to the complexity of the current drug assembly, as artemisinin is delivered to the cancer cells bound to the iron transporting protein transferrin, efforts in clinical development of the drug is slow. In this project, a protocol for the detailed structural analysis of artemisinin-transferrin complexes is proposed. By studying the solution phase structure of the drug, using state-of-the-art chiroptical spectroscopic techniques combined with cutting-edge computational chemistry, and correlating these findings with activity studies, it is hoped that the process of developing artemisinin into a viable anti-cancer drug will be stream lined before the costly (both with respect to money and time) clinical trials. Therefore, it is also envisioned that the protocol will define precedence for other pre-clinical drug studies.

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Project type(s)

  • Research Project

SusChemA. 01/01/2015 - 31/12/2020

Abstract

This project represents a research contract awarded by the University of Antwerp. The supervisor provides the Antwerp University research mentioned in the title of the project under the conditions stipulated by the university.

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  • Research Project

Towards a breakthrough in applications of vibrational optical activity: an experimental and theoretical study of the crowding effects on proteins. 01/01/2015 - 31/12/2018

Abstract

The goal of this research project is to collect experimental data on the effect of crowded environments on the structure of proteins by means of two innovative spectroscopic techniques, Raman optical activity (ROA) and vibrational circular dichroism (VCD). This experimental data will be compared to theoretical predictions of the effect, after which a conclusion about the nature and the importance of the influence of the crowding effect on the behavior of proteins in cellular environments can be drawn.

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  • Research Project

Unravelling structural motives of intrinsically unstructured proteins employing Raman optical activity: Understanding the basis of neurodegenerative diseases 01/10/2013 - 30/09/2017

Abstract

In the aging population of the Western World, age-related neurodegenerative diseases, such as Alzheimer's and Parkinson's, are becoming an ever-increasing issue. Common to these diseases are build up of protein matter in the brain, leading to degeneration of brain tissue. The proteins responsible for this degeneration belong to a group of proteins usually found on the periphery of structural biology; the intrinsically unstructured proteins (IUPs). Lacking the structural elements traditionally associated with function, IUPs were historically ignored by structural biologists as "non-functioning". In the modern age of proteomics, this group of proteins has indeed proven to be functional, but in connection with disease, it is the sudden malfunction of IUPs that is in focus. As this group of proteins lack classically defined structural elements and are highly dynamic, the usual structural characterisation tools fall short in the analysis of IUPs, and even our fundamental understanding of "structure" fails. It is therefore imperative to develop new tools, and to generate a new understanding of protein structure itself when analysing IUPs. This project aims to do exactly that: By combining state-of-the-art chiroptical spectroscopic techniques with cutting-edge computational chemistry, the world of the IUPs will be analysed in detail, redefining what constitutes protein structure and ultimately aiding the understanding of what turns a normal, functioning IUP into a pathogenic entity.

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  • Research Project

Raman optical activity as the driving force in the spin-off of 'The European Centre for Chirality ". 01/09/2013 - 31/12/2013

Abstract

This project represents a research agreement between the UA and on the onther hand IWT. UA provides IWT research results mentioned in the title of the project under the conditions as stipulated in this contract.

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Project type(s)

  • Research Project