Lars O. Baumbusch
Position: Senior scientist and project leader, MSc, PhD (Dr.)
Phone: +47 23 07 33 72
Email:
Daß ich erkenne, was die Welt im Innersten zusammenhält
So that I may perceive whatever holds the world together in its inmost folds
Johann Wolfgang von Goethe, Faust: Der Tragödie Erster Teil

 

Education and professional experience

Professional experience

11.2012 - present      Dep. of Pediatric Research (PFI), Division of Pediatric and Adolescent Medicine,
                               Oslo University Hospital (OUS) Rikshospitalet, Oslo, Norway
                               Senior scientist and project manager
05.2007 - 10.2012     Dep. of Genetics, Institute for Cancer Research and Dep. of Pathology,
                               Oslo University Hospital Radiumhospitalet, Oslo, Norway
                               Scientist and project group leader
09.2006 - 06.2010     Biomedical Research group, Dep. of Informatics, University of Oslo, Norway
                               Adjunct associate professor (equivalent førsteamanuensis-II)
12.2001 - 04.2007     Dep. of Genetics, Institute for Cancer Research and Dep. of Pathology,
                               Oslo University Hospital Radiumhospitalet, Oslo, Norway
                               Post-doc

Education

01.1997 - 11.2001     Div. of Molecular Biology, Dep. of Biology, University of Oslo, Norway
                               Dr. scient. (equivalent PhD)
10.1993 - 06.1996     Dep. of Biology, Albert-Ludwig University of Freiburg, Germany
                               Diploma in Biology (equivalent MSc or cand. scient.)
10.1992 - 09.1993     Dep. of Botany, Trinity College Dublin, Ireland
                               Studies abroad and student project
10.1989 - 09.1992     Dep. of Biology, Albert-Ludwig University of Freiburg, Germany
                               Intermediate diploma in biology (equivalent BSc or cand. mag.)
04.1989 - 09.1989     Philosophical faculty, Albert-Ludwig University of Freiburg, Germany
                               Philosophical studies
08.1987 - 03.1989     St. Fidelius Parish, Offenburg, Germany
                               Civilian service
08.1978 - 05.1987     Max-Planck Gymnasium Lahr, Germany
                               Abitur (equivalent university-entrance diploma or examen artium)
08.1974 - 07.1978     Grund- und Hauptschule Sulz, Lahr, Germany
                               Primary school

Projects (selected)

01.2015 - present      Research project
                               Exploring high-risk neuroblastoma by sequencing technology (PI)
02.2009 - 12.2012     Research project
                               A pilot study for identification of regulatory long non-protein coding RNA genes inbreast cancer (PI)
01.2008 - 12.2011
    Project group

                               Molecular signatures of disseminated tumor cells in breast cancer (PI - project group leader)
05.2006 - 04.2009
    Post-doc project
                               Molecular signatures as diagnostic and therapeutic targets for disseminated epithelial malignancies
01.2003 - 06.2004
    Research project
                               A bioinformatic approach to study alternative splicing in breast tumors based on microarray data(PI)
12.2001 - 04.2006
    Post-doc project
                               A bioinformatic and genetic approach to understand gene regulation and dysregulation in breast                                tumor development and progression (career stipend from the Research Council of Norway)
01.1997 - 11.2001
    PhD-project
                               Identification and analysis of genes controlling embryogenesis
                               and embryo dormancy in plants
06.1995 - 06.1996
    Diploma project
                               The influence of ozone and UV-B on the antioxidative system of spruce (Picea abies L.)
                               under natural and controlled conditions
06.1993 - 08.1993
    Student project
                               Beans (Phaseolus vulgaris cv. Lit) as a bioindicator in an international programme
                               for evaluating the effects of air pollution on crops

 


 Research projects at the OUS Rikshospitalet

Exploring high-risk neuroblastoma by sequencing technology

Next generation sequencing will be the basis for personalized cancer medicine in the near future, in particular for heterogenic diseases with multi-modal therapy applications like neuroblastoma (NB) - one of the major challenges in pediatric oncology. We hypothesize that comparative sequencing analysis will provide means about heterogeneity and relapse in high-risk NB. Patient samples are available from an existing diagnostic biobank and novel patients will be enrolled in a Norwegian pediatric cancer sequencing biobank project. In collaboration with our scientific partners, the required technologies are in place, like aCGH and single cell aCGH, sequencing techniques, further comparative analysis of high resolution data. We are convinced that investigating the genome and transcriptome of the primary tumor, relapse tissue, and micrometastases in high-risk NB will reveal novel insight into the heterogeneity, tumor evolution, and biology of NB - a promising prospective for new therapies for children fighting NB. 

 

Novel biomarkers for neonatal asphyxia damage

Neonatal asphyxia is a severe medical condition resulting from oxygen deficiency (hypoxia) in newborn infants causing worldwide approximately 750.000 casualties per year. Infants surviving neonatal asphyxia frequently suffer from neurological complications, including cerebral palsy. Intervention strategies are limited, and there is still a lack of reliable diagnostic biomarkers for the prediction of the severity and outcome after neonatal asphyxia.We investigate various biomarkers for neonatal asphyxia damage. At our facilities, over 100 newborn piglets have been exposed to moderate or severe hypoxia followed by reoxygenation and treatment with different antioxidative agents. 

This project resulted in the following publications:

Garberg HT, Huun MU, Baumbusch LO, Åsseg-Atneosen M, Solberg R,and Saugstad OD (2017) Temporal profile of circulating microRNA after global hypoxia-ischemia in newborn piglets. Neonatology 111(2):133-139. doi: 10.1159/000449032. Epub 2016 Oct 18.

Benterud T, Ystgaard MB, Manueldas S, Pankratov L, Alfaro-Cervello C, Florholmen G, Ahmed MS, Sandvik L, Norgren S, Bjørås M, Baumbusch LO, Solberg R, Saugstad OD (2017) N-Acetylcysteine amide exerts possible neuroprotective effects in newborn pigs after perinatal asphyxia. Neonatology 111:12-21 doi: 10.1159/000447255. Epub 2016 Aug 6.

Benterud T, Pankratov L, Solberg R, Bolstad N, Skinningsrud A, Baumbusch L, Sandvik L, Saugstad OD (2015) Perinatal asphyxia may influence the level of beta-amyloid (1-42) in cerebrospinal fluid: an experimental study on newborn pigs. PLoS ONE 10(10): e0140966. doi: 10.1371/journal.pone.0140966.

 


Research projects at the OUS Radiumhospitalet

Molecular signatures of long-coding RNAs in breast cancer patients

Of the ~3.3 billion bases of the human genome, only about 2% code for proteins and until very recently, the remaining 98% have been considered to be 'junk'. However, large transcriptomic studies have shown that around 90% of the genome is actively transcribed of which a significant fraction may contribute to a previously underestimated layer of regulatory long non-coding RNAs (lncRNAs). In several studies it has been shown that the expression of small ncRNAs, like microRNAs, is associated with diseases including cancer. However, the large group of long lncRNAs has drawn less attention. LncRNA expression of selected 26 breast carcinoma samples, representing the five clinically relevant tumor expression subclasses, and 5 samples from normal breast tissue were analyzed using the nONCOchip®. The nONCOchip®, developed by the RNomics group at the Fraunhofer Institute for Cell Therapy and Immunology, covers both, experimentally identified cancer related lncRNAs as well as known or predicted non-coding RNAs from public databases. The array includes in total 243,000 probes, with over 60,000 newly identified transcripts. First results reveal that lncRNAs are variably expressed in breast tissue, expression signatures are different between breast tumors and normal breast tissues, expression patterns in breast cancer show a high degree of heterogeneity, and certain lncRNAs are significantly differentially expressed, e.g. between TP53 wild type and mutated samples. The overall aims of this study are to identify lncRNAs involved in gene regulation in breast cancer, to explore lncRNAs gene aberrations/expression profiles important for breast cancer development and progression, and to identify lncRNAs biomarkers predictive for breast cancer. As the growing list of lncRNA genes influencing carcinogenesis is striking, the identification of clinically relevant lncRNAs may open up for the development of novel biomarkers and therapeutic tools that attack diseased cells.

This project resulted in the following publication:

Reiche K, Kasack K, Schreiber S, Lüders T, Due EU, B Naume, Riis M, Kristensen VN, Horn F, Børresen-Dale A-L, Hackermüller J, and Baumbusch LO (2014) Long non-coding RNAs differentially expressed between normal versus primary breast tumor tissues disclose converse changes to breast cancer-related protein-coding genes. PLOS ONE 9(9):e106076. doi: 10.1371/journal.pone.0106076. eCollection 2014. Epub 2014 Sep 29.

 

Molecular signatures of disseminated tumor cells in breast cancer

The main focus of this project group was to explore the genomic characteristics of disseminated tumor cells in breast cancer and to allocate their relevance to clinical parameters. The critical step in breast cancer progression is the establishment of metastasis to distant organs. Circulating tumor cells (CTC) in peripheral blood and disseminated tumor cells (DTC) in secondary organs like bone marrow are considered to be rare members among the cellular population of primary tumor cells. In several studies it has been demonstrated that the presence of these cells is an independent prognostic factor and detection of DTC identifies patients with less favorable clinical outcome. However, we still lack knowledge of the genomic characteristics of DTC and how to target these cells. A reason for this limitation has been a deficiency of procedures allowing high-resolution analyses of CTC/DTC, including DNA-copy number changes. Due to the implementation of a state-of-the-art technique, called single cell array comparative genomic hybridization (SCaCGH), we are finally able to perform in-depth analysis of occult circulating tumor cells on various high density array platforms. Further, new tools for detection and characterization of CTC/DTC including qRT-PCR have been developed. Genotyping and phenotyping of occult tumor cells will provide information to better understand tumor initiation, tumor heterogeneity, and subsequent metastasis formation. Using novel bioinformatic and biostatistical tools studied in connection with a detailed primary tumor analysis, we wish to identify biological markers and genes responsible for the capacity of cancer cells to metastasize. This may be clinically useful as evidence for an early occult spread of tumor cells, as a relevant prognostic factor, and finally, permit direct exploration of markers for targeted treatment. The project was supported by DISMAL. The main objective of DISMAL was to improve specificity and sensitivity of current platforms for DTC (disseminated tumor cells) detection in patients with epithelial tumors. The Goal was to identify novel markers at the DNA, RNA or protein level that allows a more precise detection of DTC with a high risk for metastatic progression. The project was an integrative part of the Breast Cancer study in the Micrometastasis project ongoing at the Norwegian Radium Hospital. The work was performed in close collaboration between the Dep. of Pathology and the Dep. of Genetics.

This project resulted in the following publications:

Demeulemeester J*, Kumar P*, Møller EK*, Nord S, Wedge DC, Peterson A, Mathiesen RR, Fjelldal R, Esteki MZ, Theunis K, Gallardo EF, Grundstad JA, Borgen E, Baumbusch LO, Børresen-Dale A-L, White KPKristensen VN, van Loo P, Voet T, and Naume B (2017) Tracing the origin of disseminated tumor cells in breast cancer using single-cell sequencing.Genome Biology 17:250. doi:10.1186/s13059-016-1109-7.

Møller EK, Kumar P, voet T, Peterson A, van Loo P, Mathiesen RR, Fjelldal R, Grundstad J, Borgen E, Baumbusch LO, Naume B, Børresen-Dale A-L, White KP, Nord S, and Kristensen VN (2013) Next generation sequencing of disseminated tumor cells. Frontiers in Molecular and Cellular Oncology. doi: 10.3389/fonc.2013.00320. Epub 2013 Dec 31.

Otto B, Gruner K, Heinlein C, Wegwitz F, Nollau P, Ylstra B, Pantel K, Schumacher U, Baumbusch LO, Martin-Subero JI, Siebert R, Wagener C, Streichert T, Deppert W, and Tolstonog GV (2013) Low-grade and high-grade mammary carcinomas in WAP-T transgenic mice are independent entities distinguished by Met expression. International Journal of Cancer 132 (6):1300-10. doi:10.1002/ijc.27783. Epub 2012 Sep 26.

Mathiesen RR, Fjelldal R, Due EU, Geigl JB, Riethdorf S, Knut Liestøl, Borgen E, Rye IH, Schneider IJ,  Obenauf AC, Mauermann O, Nilsen G, Lingjærde OC, Børresen-Dale A-L, Pantel K, Speicher MR, Naume B, and Baumbusch LO (2012) High resolution analysis of copy number changes in disseminated tumor cells of patients with breast cancer. International Journal of Cancer 131 (4): E405-15. doi: 10.1002/ijc.26444. Epub 2011 Nov 9.

Molloy TJ, Bosma AJ, Baumbusch LO, Synnestvedt M, Borgen E, Russnes HG, Schlichting E, van't Veer L, and Naume B (2011) The prognostic significance of tumor cell detection in the peripheral blood  versus the bone marrow in 774 early-stage breast cancer patients. Breast Cancer Research 13 (3): R61.doi: 10.1186/bcr2898.

Geigl JB, Obenauf AC, Waldispuehl-Geigl J, Fischer M, Trajanoski Z, Baumbusch LO, Speicher MR (2009) Identification of small gains and losses in single cells after whole genome amplification on tiling oligo arrays. Nucleic Acids Research 37(15):e105. doi: 10.1093/nar/gkp526. Epub 2009 Jun 18.

 

Prosjektbeskrivelse på norsk

Genomic instability

Genomic instability is a hallmark of malignant tumours, causing disturbed integrity of the genome, numerical alterations, and structural changes. For various cancer types genomic instability has been associated with poor prognosis, suggesting that genomic instability may confer growth advantage of cancer cells. In most cancer types, genomic instability is characterized by copy number alterations, allelic imbalance, or the loss of heterozygosity. The molecular basis of genomic instability remains still unclear; however, mutations in key checkpoint proteins and DNA repair genes are supposed to be involved. Interestingly, the effects of disordered genomic organization may also have an unfavourable effect on the overall viability and fitness of cancer cells. Precise delineation of the negative and positive effects of genomic instability on cancer cells is of potentially great importance for tumour classification, survival prediction, and individualized therapy. The research is focused on the assessment of genomic instability in a variety of tumour types by applying various methods or the developing novel algorithms.This work includes projects about the complexity and genomic aberrations in breast tumors and serous ovarian cancers; integrated omics analysis; efficient algorithms for single- and multi-track copy number segmentation analysis; genomic architecture; comparison of platforms and algorithms for classification of copy number alterations in human breast tumors.

This project resulted in the following publications:

Kaveh F*, Baumbusch LO*, Nebdal D, Børresen-Dale A-L, Lingjærde OC, Edvardsen H, Kristensen VN, and Solvang HK (2016) A systematic comparison of copy number alterations in four types of female cancer. BMC Cancer 16(1):913. doi: 10.1186/s12885-016-2899-4. Epub 2016 Nov 22.

Liu Y*, Zhou R*, Baumbusch LO, Tsavachidis S, Brewster AM, Do K-A, Sahin A, Hortobagyi GN, Taube JH, Mani SA, Aarøe J, Wärnberg F, Børresen-Dale A-L, Mills GB, Thompson PA, and Bondy ML (2014) Genomic copy number imbalances associated with bone and non-bone metastasis of early-stage breast cancer. Breast Cancer Research and Treatment. doi: 10.1007/s10549-013-2796-3. Epub 2013 Dec 4.

Baumbusch LO*, Helland Å*, Wang Y, Liestøl K, Schaner ME, Holm R, Etemadmoghadam D, Alsop K, Brown P, AOCS Group, Mitchell G, Fereday S, Defazio A, Bowtell DDL, Kristensen GB, Lingjaerde OC, and Børresen-Dale A-L (2013) High levels of genomic aberrations in serous ovarian cancers are  associated with better survival. PLoS ONE 8 (1):e54356. doi: 10.1371/journal.pone.0054356. Epub 2013 Jan 23.

Aure MR*, Steinfeld I*, Baumbusch LO*, Liestøl K, Lipson DK, Naume B, Kleivi K, Kristensen VN, Børresen-Dale AL, Lingjærde OC, and Yakhini Z (2013) Identifying in-trans process associated genes in breast cancer by integrated analysis of copy number and expression data. PLoS ONE 8 (1):e53014. doi:10.1371/journal.pone.0053014. Epub 2013 Jan 30.

Nilsen G, Listøl K, van Loo P, Vollan HKM, Eide MB, Rueda OM, Chin S-F, Russell R, Baumbusch LO, Caldas C, Børresen-Dale A-L, and Lingjærede OC (2012) Copynumber: Efficient algorithms for single- and multi-track copy number segmentation analysis. BMC Genomics 13:591. doi: 10.1186/1471-2164-13-591. Epub 2012 Nov 4.

Russnes HG*, Vollan HKM*, Lingjærde OC, Krasnitz A, Lundin P, Naume B, Sørlie T,  Borgen E, Rye IH, Langerød A, Chin S-F, Teschendorff AE, Stevens PJ, Månér S, Schlichting E, Baumbusch LO, Kåresen R, Stratton MP, Wigler M, Caldas C, Zetterberg A, Hicks J, and Børresen-Dale A-L (2010) Genomic architecture characterizes tumor progression paths and fate in breast cancer patients. Translational Science 2 (38): 38ra47. doi: 10.1126/scitranslmed.3000611.

(The marked authors should be considered as joint first(*) or senior(‡) authors)

 

Prosjektbeskrivelse på norsk

 


Post-doc projects at the OUS Radiumhospitalet

A bioinformatic and genetic approach to understand gene regulation and dysregulation in breast tumor development and progression

The aim of this project was to a.) Establish, evaluate and possibly develop new bioinformatical tools to handle the massive data obtained from microarray experiments to compare gene expression- with gene copy number data from classical and various array based CGH analyses b.) Identify and characterize genes that are dysregulated by other mechanisms than copy number alterations c.) Analyze the impact of the above identified genes (or gene clusters) on clinical parameters and patient outcome d.) Analyze experimentally the role of mRNA binding proteins using CRD-BP and MYC genes as a model system, and search for similar protein motifs and investigate their role in breast tumorigenesis. Microarray-based Comparative Genome Hybridization (array CGH) provides the possibility to connect DNA copy-aberrations with genomic map positions. Different types of arrays may be used in such analyses, cDNA, BAC arrays containing genomic DNA or oligoarrays. In close collaboration with the Bioinformatics group, Institute of Informatics (University of Oslo), UCSF and the Stanford University a comparative study of the different methods is performed based on state-of-the-art statistical modeling and analysis methods. This project was supported by FUGE.

This project resulted in the following publications:

Baumbusch LO, Aarøe J, Hicks J, Johansen FE, Sun H, Bruhn L, Gunderson K, Naume B, Kristensen VN, Listøl K, Børresen-Dale A-L and Lingjærede OC (2008) Comparison of the Agilent, ROMA/NimbleGen, and Illumina platforms for classification of copy number alterations in human breast tumors. BMC Genomics 8; 9(1):379.

Ben-Dor A, Lipson D, Tsalenko A, Reimers M, Baumbusch LO, Barrett MM, Weinstein J, Børresen-Dale A-L, Yakhini Z (2007) Framework for identifying common aberrations in DNA copy number data. In: Research in Computational Molecular Biology. Volume 4453. Springer, Berlin / Heidelberg: 122-136.

Lingjærde OC, Baumbusch LO, Liestøl K, Glad I and Børresen-Dale AL (2005) CGH-Explorer: a program for visualization and analysis of CGH-array data. Bioinformatics 21(6): 821-822.

(*These authors should be considered as shared first authors)

 

A bioinformatic approach to study alternative splicing in breast tumors based on microarray data

The biological dogma of a simple genetic flow of information from DNA via RNA to protein expression is on its way to disband. A manifold picture of a comprehensive and interactive regulatory system with multiple regulatory mechanisms is evolving, including non-coding RNAs, infrastructural RNAs and alternative splicing processes. Signaling proteins, RNA processing and RNA binding are frequent signals in the targeting of chromatin complexes and in the regulation of gene expression during differentiation and development. A common feature for all these regulation mechanisms is a partial or complete independence of consistency to gene copy numbers. Such uncommon regulatory features can be identified by utilizing microarray datasets, where microarray comparative genomic hybridization (array CGH) analysis of copy number variation has been performed in parallel with microarray gene expression studies. The growing list of unconventional gene regulation mechanisms is striking and we hypothesize that many of them are present and dysregulated in cancer. This seems to be not only to be an interesting feature for cancer diagnostic and therapeutic issues but also for the biological understanding of the mechanisms of gene regulating as such.

This project resulted in the following publication:

Baumbusch LO, Myhre S, Langerød A, Bergamaschi A, Geisler S, Lønning P-E, Deppert W, Dornreiter I and Børresen-Dale A-L (2006) Expression of wild-type and mutated p53 and its novel isoform Δp53 in breast carcinomas. Molecular Cancer 5:47, page 1-20.

 

Prosjektbeskrivelse på norsk

 


PhD project at the Dep. of Biology, UiO

Identification and analysis of genes controlling embryogenesis and embryo dormancy in plants

Prior to germination mature seeds in many higher plants undergo a period of dormancy. The dormancy stage is characterised by the temporary failure to immediately germinate under favourable conditions until specific environmental stimuli, like low temperature (stratification) and light, release this inhibition. In this thesis an attempt has been taken to form a better understanding of the genes and processes controlling embryogenesis and dormancy in plants. In screenings of EMS-mutagenized and T-DNA tagged lines several INSOMNIAC (nsm) mutants were identified that rapidly germinate in light without prior stratification. Mutants in NSM1 and NSM2 are dominant alleles; mutants at the NSM5 locus are semi-dominant alleles with an age-dependent level of penetrance. NSM1, NSM2 and NSM5 are necessary for the repression of precocious germination of immature seed in culture but not for the inhibition of vivipary. Seeds of nsm1 and nsm2 have wild-type sensitivity to abscisic acid (ABA), in contrast to the ABA-hypersensitivity of nsm5 seeds. However, all nsm mutant plants have normal vegetative and reproductive growth. Mapping of NSM genes was performed using PCR-based protocols. Several critical parameters of the standard method needed to be modified in order to provide a reliable and efficient mapping technique, including increased density of markers for various Arabidopsis ecotypes. NSM1, NSM2 and NSM5 were mapped to different loci on chromosome 5. To study the establishment, maintenance and release of dormancy the mRNA levels of LEC1, FUS3 and ABI3 were examined in various strong or moderate dormancy ecotypes and the nsm1, nsm2 and nsm5-1 and abi3-1 mutants. Observed marginal variations in mRNA levels of the various markers show no obvious correlation to differences in dormancy levels. Analysis of ABI3, AtEm1 and AtEm6 expression in Ws wild-type and nsm mutant seeds exposed to variable conditions of light, temperature and afterripening revealed reduced AtEm1 and AtEm6 and altered ABI3 mRNA levels in nsm mutants. However, changes due to temperature and light factors are similar to those that occur in Ws wild-type seeds. An alternative approach performed to identify embryogenesis regulators is survey of candidate genes. In this respect SET domain genes, demonstrated to be multifunctional chromatin regulators, have been examined in the Arabidopsis genome. 37 AtSET domain genes have been identified of which at least 29 are functional genes, mainly expressed in buds, flowers and seeds. The expression patterns and the high numbers of SET domain proteins in Arabidopsis may reflect their complex regulatory role in plant development and a putative function in the process of dormancy.

This thesis resulted in the following publications:

Baumbusch LO (2006) Genetic control of plant embryogenesis and embryo dormancy in Arabidopsis thaliana. In: Floriculture, Ornamental and Plant Biotechnology: Advances and Topical Issues. Volume 1. 1st ed.. Edited by Teixeira da Silva JA. Global Science Books, London: 417-428. ISBN: 4-903313-00-X. (Review).

Baumbusch LO, Hughes DW, Galau GA and Jakobsen KS (2004) Levels of LEC1, FUS3, ABI3 and Em expression reveals no correlated with dormancy in Arabidopsis. Journal of Experimental Botany 394: 77-87.

Baumbusch, LO (2001) Identification and analysis of genes controlling embryogenesis and embryo dormancy in plants. Thesis for the degree of Doctor Scientiarium published at the University of Oslo. Norway. ISSN 1501-7710.

Baumbusch LO*, Thorstensen T*, Krauss V, Fischer A, Naumann K, Assalkhou R, Schulz I, Reuter G, and Aalen RB (2001) The Arabidopsis thaliana genome contain at least 29 active genes encoding SET domain proteins which can be assigned to four evolutionarily conserved classes. Nucleic Acids Research 29: 4319-4333.

Baumbusch LO, Sundal IK, Hughes DW, Galau GA and Jakobsen KS (2001) Efficient protocols for CAPS-based mapping in Arabidopsis. Plant Molecular Biology Reporter 19: 137-149. (see: tair: Protocols and Lab Manuals).

Hughes DW, Baumbusch LO, Jakobsen KS and Galau GA Semi-dominant, ABA-hypersensitive mutant alleles of NSM5, an INSOMNIAC gene required for stratification-breakable seed dormancy in Arabidopsis. Plant Physiology (2001, accepted with modifications - under review by co-authors)

(*These authors should be considered as shared first authors)

 

Prosjektbeskrivelse på norsk

 


Master thesis project at the ALU Freiburg

The influence of ozone and UV-B on the antioxidative system of spruce (Picea abies L.) under natural and controlled conditions

Erhöhte Ozonkonzentrationen und erhöhte UV-B Strahlung gelten als Auslöser für die verstärkte Bildung von Sauerstoffradikalen und damit als Ursache für oxidativen Streß. Um den Einfluß von Ozon und UV-B auf das antioxidative System von Fichten (Picea abies L.) zu bestimmen, wurden Freilanduntersuchungen Experimenten unter kontrollierten Bedingungen gegenüber gestellt. Die Reaktionen des antioxidativen Systems von verschiedenen Klonfichten und Bäumen des natürlichen Bestands auf natürliche Streßbedingungen wurden längs eines Höhengradienten (800 m - 1750 m ü. NN) am Wank untersucht und mit den Effekten einer erhöhten Ozonkonzentration in Kombination mit einer moderaten UV-B Applikation verglichen (die einfache Ozonkonzentration und die Klimabedingungen des Kammerversuchs entsprachen den an der Wank Mittelstation aufgezeichneten Werten). Eine mögliche induktive Wirkung einer kurzzeitigen UV-B Bestrahlung auf das antioxidative System, die Superoxid-dismutase-Aktivität und das Wachstum von Fichtenkeimlingen wurde in einem Keimlings-versuch untersucht. Dazu wurden 10 Wochen alte Keimlinge 0 - 4 h einer UV-B Strahlung von 6,3 MED h-1 ausgesetzt. Die klimatischen und edaphischen Bedingungen in der Hochlage bewirkten im Vergleich zur Tallage eine Streßreaktion der Klone, die sich in einer Reduktion des Frischgewicht/Trockengewicht Verhältnisses, einer Abnahme des Gesamtproteingehaltes und einer drastischen Verminderung der Chlorophyll- und Carotinoidgehalte der Nadeln verdeutlichte. Trotz dieser eindeutigen Streßsymptome veränderten sich die Malondialdehydgehalte nicht. Daher erwies sich der Malondialdehydgehalt der ein Maß für Lipidoxidationen ist, als unzureichender Streß-parameter. Weiterhin war in den Nadeln das Ascorbat Redox Verhältnis auf 70% abgesunken und die Superoxiddismutase-Aktivität in der Hochlage im Vergleich zur des antioxidativen Systems an die Umweltbedingungen der Hochlage. Die Unterschiede in den Reaktionen des antioxidativen Systems verschiedener Klone auf die natürlichen Streßbedingungen in der Hochlage waren insgesamt nur geringfügig. Der Klon C 5/1/16 mit dem Vitalitätsmerkmal „gut" besaß einen signifikant höheren Glutathiongehalt als die Klone C 5/1/16 und C 4/4/8 mit den Vitalitätsmerkmalen „schlecht" und „mittel". Da die Bäume des natürlichen Bestandes in der Hochlage einen vergleichbar hohen Glutathiongehalt aufwiesen wie der vitalste Klon, scheinen erhöhte Glutathiongehalte ein Indikator für die Adaptation an Höhenstreß zu sein. Durch die kurzzeitige UV-B Bestrahlung von Keimlingen nahm der Gehalt an Glutathion in den Primärnadeln ab, während andere Komponenten des antioxidativen Systems unbeeinflußt waren. Daraus läßt sich schließen, daß der Glutathion-gehalt sehr empfindlich auf Veränderung der Umwelt reagiert. Eine Erhöhung der Ozonkonzentration in Kammerversuchen bewirkte eine Induktion des antioxidativen Systems der Fichten. Dies resultierte in erhöhten Ascorbat- und Glutathion-gehalten. Eine Kombination von erhöhtem Ozon und moderater UV-B Strahlung schwächte diese Induktion leicht ab. Die Superoxiddismutase-Aktivität wurde durch eine Erhöhung der Ozonkonzentration nicht verändert; jedoch bewirkte die UV-B Applikation eine signifikante Erhöhung der Superoxiddismutase-Aktivität um 43%. Eine gelelektrophoretische Trennung der Isoenzyme zeigte, daß das Isoenzymmuster bei den verschiedenen Behandlungs-varianten nicht verändert war. Von den 3 aufgetrennten Isoenzymen konnten die chloroplastidäre SOD I und die cytosolische SOD II identifiziert werden. Eine kurzfristige UV-B Bestrahlung hatte weder einen induktiven noch einen destruktiven Effekt auf das antioxidative System und das Wachstum von Fichtenkeimlingen. In den Primär-nadeln der Keimlinge wurden erhöhte Chlorophyll- und Carotinoidgehalte bestimmt, die Ascorbatgehalte und die Superoxiddismutase-Aktivität waren gegenüber den Kontrollen nicht verändert. Die Erhöhung der Superoxiddismutase-Aktivität durch die Applikation von UV-B bei dem Expositionsversuch scheint daher auf eine längerfristige Adaptation zurückzuführen zu sein. Bei Freilanduntersuchungen wurden Schadsymptome und Streßreaktionen an Nadeln der Bäume in der Hochlage beobachtet. Jedoch zeigten Versuche in Expositionskammern, daß das antioxidativen Systems auf erhöhtes Ozon und moderates UV-B mit einer Induktion reagierte. Ein induktiver UV-B Kurzzeiteffekt auf das antioxidativen Systems konnte ausgeschlossen werden. Im Freiland waren andere Schad- und Streßsymptome aufgetreten, als unter kontrollierten Bedingungen. Diese Ergebnisse lassen den Schluß zu, daß die Belastung des antioxidativen Systems, wie sie in der Hochlage beobachtet wurden, nicht allein durch eine Erhöhung der Ozonkonzentration und der UV-B Strahlung ausgelöst sein können. Weitere Umweltfaktoren wie niedrige Temperaturen und geringe Niederschläge sollten daher bei zukünftigen Untersuchungen ebenfalls berücksichtigt werden.

This thesis resulted in the following publications:

Polle A, Baumbusch LO, Oschinski C, Eiblmeier M, Kuhlenkamp V, Vollrath B, Scholz, F and Rennenberg H (1999) Growth and protection against oxidative stress in young clones and mature spruce trees (Picea abies L.) at high altitudes. Oecologia 121: 149-156.

Baumbusch LO, Eiblmeier M, Schnitzler J-P, Heller W, Sandermann H Jr and Polle A (1998) Interactive effects of ozone and low UV-B radiation on antioxidants in spruce (Picea abies) and pine (Pinus sylvestris) needles. Physiologia Plantarum 104: 248-254.

Baumbusch, LO (1996) Der Einfluss von Ozon und UV-B auf auf das anitoxidative System der Fichte (Picea abies L.) im Freiland und unter kontrollierten Bedingungen. Diploma thesis published at the Faculty of Biology, Albert-Ludwigs-University Freiburg, Germany.

 


Reviews

Baumbusch LO (2006) Genetic control of plant embryogenesis and embryo dormancy in Arabidopsis thaliana. In Floriculture, Ornamental and Plant Biotechnology: Advances and Topical Issues. Vol. 1. (1st ed.). Edited by Teixeira da Silva JA. Global Science Books, London: 417-428. ISBN: 4-903313-00-X.

 

Popular scientific publications

Liebers A and Baumbusch LO (2005) Tulpenrausch. Ka Gö Verlag, Heidelberg, (children fiction). ISBN 3-938440-01-5.

 



 

Author network for Lars O. Baumbusch by COREMINE medical


Publications 2016

Benterud T, Ystgaard MB, Manueldas S, Pankratov L, Alfaro-Cervello C, Florholmen G, Ahmed MS, Sandvik L, Norgren S, Bjørås M, Baumbusch LO, Solberg R, Saugstad OD (2016)
N-Acetylcysteine Amide Exerts Possible Neuroprotective Effects in Newborn Pigs after Perinatal Asphyxia
Neonatology, 111 (1), 12-21
PubMed 27497671

Demeulemeester J, Kumar P, Møller EK, Nord S, Wedge DC, Peterson A, Mathiesen RR, Fjelldal R, Zamani Esteki M, Theunis K, Fernandez Gallardo E, Grundstad AJ, Borgen E, Baumbusch LO, Børresen-Dale AL, White KP, Kristensen VN, Van Loo P, Voet T, Naume B (2016)
Tracing the origin of disseminated tumor cells in breast cancer using single-cell sequencing
Genome Biol, 17 (1), 250
PubMed 27931250

Garberg HT, Huun MU, Baumbusch LO, Åsegg-Atneosen M, Solberg R, Saugstad OD (2016)
Temporal Profile of Circulating microRNAs after Global Hypoxia-Ischemia in Newborn Piglets
Neonatology, 111 (2), 133-139
PubMed 27750254

Kaveh F, Baumbusch LO, Nebdal D, Børresen-Dale AL, Lingjærde OC, Edvardsen H, Kristensen VN, Solvang HK (2016)
A systematic comparison of copy number alterations in four types of female cancer
BMC Cancer, 16 (1), 913
PubMed 27876019

Publications 2015

Benterud T, Pankratov L, Solberg R, Bolstad N, Skinningsrud A, Baumbusch L, Sandvik L, Saugstad OD (2015)
Perinatal Asphyxia May Influence the Level of Beta-Amyloid (1-42) in Cerebrospinal Fluid: An Experimental Study on Newborn Pigs
PLoS One, 10 (10), e0140966
PubMed 26501201

Gul KA, Øverland T, Osnes L, Baumbusch LO, Pettersen RD, Lima K, Abrahamsen TG (2015)
Neonatal Levels of T-cell Receptor Excision Circles (TREC) in Patients with 22q11.2 Deletion Syndrome and Later Disease Features
J Clin Immunol, 35 (4), 408-15
PubMed 25814142

Publications 2014

Reiche K, Kasack K, Schreiber S, Lüders T, Due EU, Naume B, Riis M, Kristensen VN, Horn F, Børresen-Dale AL, Hackermüller J, Baumbusch LO (2014)
Long non-coding RNAs differentially expressed between normal versus primary breast tumor tissues disclose converse changes to breast cancer-related protein-coding genes
PLoS One, 9 (9), e106076
PubMed 25264628

Publications 2013

Aure MR, Steinfeld I, Baumbusch LO, Liestøl K, Lipson D, Nyberg S, Naume B, Sahlberg KK, Kristensen VN, Børresen-Dale AL, Lingjærde OC, Yakhini Z (2013)
Identifying in-trans process associated genes in breast cancer by integrated analysis of copy number and expression data
PLoS One, 8 (1), e53014
PubMed 23382830

Baumbusch LO, Helland Å, Wang Y, Liestøl K, Schaner ME, Holm R, Etemadmoghadam D, Alsop K, Brown P, Australian Ovarian Cancer Study Group, Mitchell G, Fereday S, DeFazio A, Bowtell DD, Kristensen GB, Lingjærde OC, Børresen-Dale AL (2013)
High levels of genomic aberrations in serous ovarian cancers are associated with better survival
PLoS One, 8 (1), e54356
PubMed 23372714

Liu Y, Zhou R, Baumbusch LO, Tsavachidis S, Brewster AM, Do KA, Sahin A, Hortobagyi GN, Taube JH, Mani SA, Aarøe J, Wärnberg F, Børresen-Dale AL, Mills GB, Thompson PA, Bondy ML (2013)
Genomic copy number imbalances associated with bone and non-bone metastasis of early-stage breast cancer
Breast Cancer Res Treat, 143 (1), 189-201
PubMed 24305980

Møller EK, Kumar P, Voet T, Peterson A, Van Loo P, Mathiesen RR, Fjelldal R, Grundstad J, Borgen E, Baumbusch LO, Naume B, Børresen-Dale AL, White KP, Nord S, Kristensen VN (2013)
Next-generation sequencing of disseminated tumor cells
Front Oncol, 3, 320
PubMed 24427740

Publications 2012

Nilsen G, Liestøl K, Van Loo P, Moen Vollan HK, Eide MB, Rueda OM, Chin SF, Russell R, Baumbusch LO, Caldas C, Børresen-Dale AL, Lingjaerde OC (2012)
Copynumber: Efficient algorithms for single- and multi-track copy number segmentation
BMC Genomics, 13, 591
PubMed 23442169

Otto B, Gruner K, Heinlein C, Wegwitz F, Nollau P, Ylstra B, Pantel K, Schumacher U, Baumbusch LO, Martin-Subero JI, Siebert R, Wagener C, Streichert T, Deppert W, Tolstonog GV (2012)
Low-grade and high-grade mammary carcinomas in WAP-T transgenic mice are independent entities distinguished by Met expression
Int J Cancer, 132 (6), 1300-10
PubMed 22907219

Publications 2011

Mathiesen RR, Fjelldal R, Liestøl K, Due EU, Geigl JB, Riethdorf S, Borgen E, Rye IH, Schneider IJ, Obenauf AC, Mauermann O, Nilsen G, Christian Lingjaerde O, Børresen-Dale AL, Pantel K, Speicher MR, Naume B, Baumbusch LO (2011)
High-resolution analyses of copy number changes in disseminated tumor cells of patients with breast cancer
Int J Cancer, 131 (4), E405-15
PubMed 21935921

Molloy TJ, Bosma AJ, Baumbusch LO, Synnestvedt M, Borgen E, Russnes HG, Schlichting E, van't Veer LJ, Naume B (2011)
The prognostic significance of tumour cell detection in the peripheral blood versus the bone marrow in 733 early-stage breast cancer patients
Breast Cancer Res, 13 (3), R61
PubMed 21672237

Publications 2010

Lingjærde OC, Krasnitz A, Lundin P, Naume B, Sørlie T, Borgen E, Rye IH, Langerød A, Chin SF, Teschendorff AE, Stephens PJ, Månér S, Schlichting E, Baumbusch LO, Kåresen R, Stratton MP, Wigler M, Caldas C, Zetterberg A, Hicks J, Børresen-Dale AL (2010)
Genomic architecture characterizes tumor progression paths and fate in breast cancer patients
Sci Transl Med, 2 (38), 38ra47
PubMed 20592421

Publications 2009

Geigl JB, Obenauf AC, Waldispuehl-Geigl J, Hoffmann EM, Auer M, Hörmann M, Fischer M, Trajanoski Z, Schenk MA, Baumbusch LO, Speicher MR (2009)
Identification of small gains and losses in single cells after whole genome amplification on tiling oligo arrays
Nucleic Acids Res, 37 (15), e105
PubMed 19541849

Publications 2008

Baumbusch LO, Aarøe J, Johansen FE, Hicks J, Sun H, Bruhn L, Gunderson K, Naume B, Kristensen VN, Liestøl K, Børresen-Dale AL, Lingjaerde OC (2008)
Comparison of the Agilent, ROMA/NimbleGen and Illumina platforms for classification of copy number alterations in human breast tumors
BMC Genomics, 9, 379
PubMed 18691401

Publications 2006

Baumbusch LO, Myhre S, Langerød A, Bergamaschi A, Geisler SB, Lønning PE, Deppert W, Dornreiter I, Børresen-Dale AL (2006)
Expression of full-length p53 and its isoform Deltap53 in breast carcinomas in relation to mutation status and clinical parameters
Mol Cancer, 5, 47
PubMed 17054774

Publications 2004

Baumbusch LO, Hughes DW, Galau GA, Jakobsen KS (2004)
LEC1, FUS3, ABI3 and Em expression reveals no correlation with dormancy in Arabidopsis
J Exp Bot, 55 (394), 77-87
PubMed 14676287

Lingjaerde OC, Baumbusch LO, Liestøl K, Glad IK, Børresen-Dale AL (2004)
CGH-Explorer: a program for analysis of array-CGH data
Bioinformatics, 21 (6), 821-2
PubMed 15531610

Publications 2001

Baumbusch LO, Thorstensen T, Krauss V, Fischer A, Naumann K, Assalkhou R, Schulz I, Reuter G, Aalen RB (2001)
The Arabidopsis thaliana genome contains at least 29 active genes encoding SET domain proteins that can be assigned to four evolutionarily conserved classes
Nucleic Acids Res, 29 (21), 4319-33
PubMed 11691919

Publications 1999

Polle A, Baumbusch LO, Oschinski C, Eiblmeier M, Kuhlenkamp V, Vollrath B, Scholz F, Rennenberg H (1999)
Growth and protection against oxidative stress in young clones and mature spruce trees (Picea abies L.) at high altitudes
Oecologia, 121 (2), 149-156
PubMed 28308554

Publications 1998

Baumbusch LO, Eiblmeier M, Schnitzler JP, Heller W, Sandermann H, Polle A (1998)
Interactive effects of ozone and low UV-B radiation on antioxidants in spruce (Picea abies) and pine (Pinus sylvestris) needles
Physiol Plant, 104 (2), 248-254
PubMed 28244603