Frank Kjeldsen is Professor in the Department of Biochemistry and Molecular Biology at the University of Southern Denmark. Since 2001, he has held a variety of academic research positions in Denmark and Sweden. He completed his Ph.D. followed by a post-doctoral study (2001-2006) with Prof. Roman A. Zubarev (Karolinska, Sweden), and acquired advanced experience in peptide and protein characterization in biological mass spectrometry. In 2006, he received a two-year post-doctoral fellowship from the Danish Research Council to pursue a research program in chemical/biological mass spectrometry in the Department of Biochemistry and Molecular Biology (BMB) with emphasis on the fundamental aspects of peptide dissociation techniques in the negative ion-mode. In this connection, he was awarded the Danish Independent Research Councils’ Young Researcher’s Award. Later, as a recipient of the prestigious Steno grant in 2009, he obtained an associate professor position at BMB. During this time, he built his own research group and pursued independent research in the area of biological mass spectrometry. In 2012, he received two research grants to continue the studies of the application of a novel dimetalic compound in phosphoproteomics including development of supporting bioinformatics. In 2014 he was awarded one of the most prestigious awards in Europe (European Research Council´s (ERC) Consolidator award). Frank Kjeldsen´s research is focused upon three subjects: 1) fundamental understanding of fragmentation techniques for peptide/protein sequencing, 2) advances in database searching of large data sets, and 3) studies of metal-protein interactions in biological systems. To data, this work has resulted in >50 peer reviewed publications in international journals, 3 patents, and presentations at >25 national and international conferences and academic institutions. Together with collaborators, he has pioneered several novel fragmentation techniques and analytical methods (e.g., Hot Electron Capture Dissociation, Electron Detachment Dissociation, and Di-metal Phosphate Ester Stabilization). He participates in both national and international research collaborations, serve to peer-review manuscripts for scientific journals, review grant proposals for various agencies, and evaluate candidates for academic positions at other universities.
Biological mass spectrometry
To assess detailed biological information on pathways, mechanisms of regulation and post-translational modifications, mass spectrometry-based (MS) proteomics has become the leading technology. The human body is very complex and contains an estimated 20,000 genes. Additional complexity is presented by the extent of post-translational modifications (PTM) to the proteins. More than 200 different types of PTMs have been identified, including the commonly encountered phosphorylations, glycosylations, acetylations, methylations, etc. Due to the sub-stoichiometric levels and the lability of many PTMs growing attention has been paid to the robustness and reliability of MS-based protein identification strategies.
We exercise research to develop new technologies and applications in proteomics to achieve more efficient and detailed characterization of proteins and their modifications in biological systems. This will be achieved through research in three areas including, comprehensive understanding of peptide fragmentation, advances in database searching, and application of novel chemistries to proteomics. These three areas overlap and knowledge from one area can strengthen research in the others.
Frank Kjeldsen is also heading the project “METALS”.
This project has received funding from the European Research Council (ERC) under the European
Union’s Horizon 2020 research and innovation programme (grant agreement No 646603)
A graduate student or postdoctoral-fellow in my group can expect to receive training in advanced mass spectrometry-based proteomics, peptide/protein chemistry, and chemical biology. During the study you will become significantly exposed to one or more of the following specialties: mass spectral interrogation, bioinformatics, quantitative proteomics, nano-bio interactions, cell culturing/biochemical assays, gas-phase peptide chemistry, metal catalysis, and peptide synthesis.
The Kjeldsen Lab is constantly seeking highly motivated and qualified candidates that can contribute to the research activities. Please contact me if you have questions or potential ideas for projects in my group.
Tandem mass spectrometry and peptide fragmentation
Understanding peptide fragmentation patterns provide the basis to explain some of the many fragment ions in tandem mass spectra (MS/MS). MS/MS spectra contain on average 100-200 peaks of which 10-20 are peptide sequence specific fragment ions. These ions are usually identified when searched against common databases. Although most of the remaining peaks in a peptide MS/MS spectrum are due to noise and chemical decompositions a large number of peptide specific information without counterparts in existing databases remain unexplained. Recently, we have initiated a number of studies to extend the use of MS/MS information to advance database searching. For instance, using high-mass accuracy and consecutively obtained ETD and higher-energy collisional dissociation (HCD) tandem mass spectrometry to reveal amino acid composition of peptides and to infer sequence tags. In other studies we address the extensive presence of co-isolated peptides observed in MS/MS spectra (>50% of all MS/MS spectra are “contaminated” with other peptide ions) by embarking on the complementarity between certain fragment ions. Using this approach we can extract sequence specific fragment ions of both target and co-isolated peptides as well as increasing the quantitative output (termed the SuperQuant approach).
Dimetal Phosphate Ester Stabilization (DIMPES)
Application of novel chemistries in proteomics is an exciting field that certainly has the potential to solve many current challenges.
While sequencing of non-modified peptide ions with CAD MS/MS is becoming routine, phosphopeptide analysis remains a challenge. The predominant reason for this is the significant instability of the phosphate ester bond in vibrational excitation of phosphopeptide ions. The the result is facile phosphate ester group detachment (e.g. as H3PO4) from phosphorylated peptide ions and reliable determination of the phosphorylation site is hence complicated. A novel invention by myself and collaborators revealed evidence in CAD for increased phosphate ester bond stabilization in peptide ions achieved by conjugation of the phosphate motif with a novel gallium dimetal complex. We have investigated the mechanism behind this phenomenon using physical chemistry techniques as well as mass spectrometry and theoretical chemistry. Recently we have demonstrated that charge inversion and enhanced sequence information is possible using the digallium conjucation to a number of phosphatidyl inositols. Currently we are collaborating with Prof. Börje Sellergren from Malmø University to develop a method for enrichment of digallium conjugated biological molecules.
Cellular responses to nano-sized metals
In addition to basal human uptake of trace metals for proper enzyme functions, humans are exposed to an increasing amount of artificial metals encountered via consumer products, food packages, and cosmetics. Studies of dose, size, solubility, and redox potential of nano-metal particles are of high priority in the EU and among other health organizations. Nanoparticles have sizes comparable to proteins and other biomolecules and are known to accumulate in human tissues. The chemical properties of the metal nanoparticles determine the protein interactions and eventually toxicity. Studies that can reveal these interactions are urgently needed to assess potential health risks. Such studies include examination of biodistribution and surface characteristics, identification of protein interaction partners, and analysis of post-translational modifications. We are engaged in assessing these features in a number of cell models in order to obtain biological detailed information based on changes to the human proteome upon nanoparticle exposure.
Overcoming the Instability of Gaseous Peptide Phosphate Ester Groups by Metal Complexation
Svane, S.; Kryuchkov, F.; McKenzie C., Kjeldsen, F., Ang. Chemie In t. Ed. 2012, 13, 3216–3219
SuperQuant: a Data Processing Approach to Increase Quantitative Proteome Coverage
Gorshkov, V.; Verano-Braga, T.; Kjeldsen, F. Anal. Chem. 2015, 87 (12), pp 6319–6327
Insights into the Cellular Response Triggered by Silver Nanoparticles using Quantitative Proteomics
Verano-Braga, T; Miethiling-Graff, R.; Wojdyla, K.; Rogowska-Wrzesinska, A.; Brewer, J. R.; Erdmann, H.; Kjeldsen, F. ACS Nano, 2014, 8, 2161-75.
A full list of publications by professor Frank Kjeldsen can be found here.