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Henriette Aksnes's picture
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Monica Hellesvik

I am a neuro-focused cell biologist specializing in the actin cytoskeleton, the cell’s secretory pathway and the protein modification N-terminal acetylation - and I have an interest in neurodegenerative diseases. 

CURRENTLY I WORK WITH 

How do protein modifications affect our brain? 

One of the proteins that I characterized during my doctorate in the Arnesen lab was not extensively described at that time. It became clear that this enzyme had a role in the cells' secretory system and in addition there were some vague indications that it could be very important for nerve cells, something I took a special interest in since I have a background in molecular neuroscience from the Bramham lab. Through a new collaboration with neurologists at UCL, I am now uncovering clear evidence that this protein has a critical function in the brain. I am currently studying cells that are isolated from patients. These patients suffer from hereditary neurological disease because they lack a specific type of protein modification. This is incredibly exciting because we are on a track where it may be possible to describe how molecular mechanisms caused by a protein inside the brain cells have a crucial neurobiological significance. There is reason to believe that there may be a link between NAT enzymes and neurodegenerative diseases such as Parkinson's. This is something I am passionate about studying further. The incidence of neurodegenerative diseases is increasing, while the treatment has major challenges. There is therefore an urgent need for research in this area. I hope that I, through my combined specialization in NAT enzymes and molecular neuroscience, will be able to contribute to filling this knowledge gap. 

Could the lack of actin N-terminal modification in cancer be linked to an increased risk of metastasis? 

During my postdoctoral period, I was involved in characterizing an enzyme, called NAA80, which modifies the actin N-terminus. Actin is one of the most abundant proteins in our cells and it is the building block of the microfilament cell skeleton. This cytoskeleton is not rigid and static as the name might suggest, but is extremely dynamic and this constant change is, amongst other things, the basis of cell motility. Normally, in a fully developed organism, the motility of our cells is kept in check so that a liver cell maintains its position in the liver and a kidney cell maintains its position in the kidney. But in cancer, the regulation can be disturbed and this can cause cancer cells to start invading neighboring tissues and migrate to other places in the body, so-called metastasis. I got particularly interested in this process when we discovered that by removing the NAA80 enzyme, cell properties changed to become hypermobile. Recently, together with students, I have fine-tuned tools to study this process as well as further described that the Golgi apparatus is fragmented in NAA80-lacking cells.

 

    Henriette's research communication and media coverage

    Courses

    BMED320 - Methods in Medical Cell Biology

                     Research and laboratory training for project assignments at Master's level.

    MOL270 - Bioethics 

                   Guestlecturer under the theme Modelorganisms.

    MOL231 - Project in Molecular Biology

                   Research and laboratory training for project assignments at Bachelor's level.

     

    Student supervision

    2020 –        Co-supervisor for PhD candidate, Dept. of Biomedicine, UiB. Monica Hellesvik.

    2020–         Main supervisor for MSc thesis stud., Dept. of Biomedicine, UiB. Alessia Caiella.

    2020–         Main supervisor for MSc thesis stud., Dept. of Biomedicine, UiB. Liv S. Krogstad.

    2020–         Co-supervisor for MSc thesis stud., Dept. of Biological sciences, UiB. Ine Kjosås.

    2019–20     Main supervisor for MSc thesis stud., Dept. of Biomedicine, UiB. Kristine H. Furre.

    2019–20     Main supervisor for MSc thesis stud., Dept. of Biomedicine, UiB. Hanne Øye.

    2018–19     Main supervisor for MSc thesis stud., Dept. of Biological Sciences, UiB, Monica Hellesvik.

    2019–19     Main supervisor for MSc thesis stud., UiB/Universität Stuttgart, Tobias B. Beigl

    2019–19     Main supervisor for 2 BSc students in MOL231 project course, Dept. of Biological Sciences, UiB, Ine Kjosås and Emilie Seljeseth.

    2018–18     Main supervisor for 2 MSc students in BMED320 project course, Dept. of Biomedicine, UiB. Atefeh Kianian and Kristine H. Furre.

    2018–18     Main supervisor for MSc ERASMUS stud., Dept. of Biomedicine, UiB, Tobias B. Beigl.

    2014–17     Co-supervisor for PhD candidate, Dept. of Molecular biology, UiB, Marianne Goris.

    2013–16     Co-supervisor for PhD candidate, Dept. of Molecular biology, UiB, Sylvia Varland.

    2012–16     Co-supervisor for PhD candidate, Dept. of Molecular biology, UiB, Camilla Osberg.

    2011–12     Co-supervisor for MSc thesis stud., Dept. of Molecular biology, UiB, Camilla Osberg.

    2011–12     Co-supervisor for MSc thesis stud., Dept. of Molecular biology, UiB, Sylvia Varland.

    2011–12     Co-supervisor for BSc stud., Dept. of Molecular biology, UiB, Eilen Henriksen.

    Academic article
    • 2020. N-terminal acetylation of actin by NAA80 is essential for structural integrity of the Golgi apparatus. Experimental Cell Research. 1-9.
    • 2020. Exploiting the potential of commercial digital holographic microscopy by combining it with 3D matrix cell culture assays. Scientific Reports. 1-14.
    • 2018. NAA80 is actin’s N-terminal acetyltransferase and regulates cytoskeleton assembly and cell motility. Proceedings of the National Academy of Sciences of the United States of America. 4399-4404.
    • 2018. N-terminal acetylation levels are maintained during acetyl-CoA deficiency in Saccharomyces cerevisiae. Molecular & Cellular Proteomics. 2309-2323.
    • 2018. Actin polymerization and cell motility are affected by NAA80-mediated posttranslational N-terminal acetylation of actin. Communicative & Integrative Biology.
    • 2017. Molecular determinants of the N-Terminal acetyltransferase Naa60 anchoring to the Golgi membrane. Journal of Biological Chemistry. 6821-6837.
    • 2016. Microscopy-based Saccharomyces cerevisiae complementation model reveals functional conservation and redundancy of N-terminal acetyltransferases. Scientific Reports. 10 pages.
    • 2015. Molecular, cellular, and physiological significance of N-terminal acetylation. International Review of Cell and Molecular Biology. 267-305.
    • 2015. An organellar Nα-acetyltransferase, Naa60, acetylates cytosolic n termini of transmembrane proteins and maintains golgi integrity. Cell reports. 1362-1374.
    • 2013. N-Terminal Acetylation by NatC Is Not a General Determinant for Substrate Subcellular Localization in Saccharomyces cerevisiae. PLOS ONE. 7 pages.
    • 2011. The human N-Alpha-Acetyltransferase 40 (hNaa40p/hNatD) is conserved from yeast and N-terminally acetylates histones H2A and H4. PLOS ONE. 11 pages.
    Lecture
    • 2015. Metabolic Regulation of N-Terminal Acetylation in Saccharomyces cerevisiae.
    Academic lecture
    • 2020. Spying on the cells using holographic live cell imaging - revealing increased metastatic potential for cancer cells lacking NAA80 (Talk by Monica Hellesvik selected from Abstracts) .
    • 2020. Efficient and crucial quality control of HAP1 cell ploidy status (Talk selected from abstracts).
    • 2019. Knockout of the posttranslational actin modifier NAA80/NatH cause Golgi fragmentation (Talk selected from abstract).
    • 2019. Actin N-terminal acetylation impacts Golgi structural integrity (Talk by Tobias B. Beigl selected from abstracts).
    Short communication
    • 2015. Holding it together: Naa60 at the Golgi. OncoTarget. 15726-15727.
    Masters thesis
    • 2020. The Impact of N-terminal Acetylation on Actin Polymerization and Cell Migration.
    • 2020. Impact of Actin N-terminal Acetylation on Small Cell Lung Carcinoma Cell Invasiveness.
    • 2009. Time-lapse imaging of Arc/Arg3.1 protein degradation in hippocampal neurons using the novel photoconvertible fluorescent protein Dendra2.
    Doctoral dissertation
    • 2014. N-terminal acetyltransferases NatC and NatF: cellular functions and substrates.
    Poster
    • 2020. The Impact of NAA80 and Actin N-terminal Acetylation on Drug Sensitivity.
    • 2020. Spying on the cells using holographic live cell imaging - revealing increased metastatic potential for cancer cells lacking NAA80 .
    • 2020. Impact of N‐terminal acetylation on cancer cell invasiveness.
    • 2020. Efficient and crucial quality control of HAP1 cell ploidy status.
    • 2019. NAA80 KO cells – Fast and Furious? Actin N-terminal acetylation by NatH/NAA80 affects cell adhesion and early cell spreading.
    • 2019. Knockout of the posttranslational actin modifier NAA80/NatH cause Golgi fragmentation.
    • 2019. Impact of actin N-terminal acetylation.
    • 2019. Actin N-terminal acetylation impacts Golgi structural integrity.
    • 2018. Saccharomyces cerevisiae growth assays and proteomics reveal functional conservation, redundancy and substrates of N-terminal acetyltransferases.
    • 2018. N-terminal acetylation of actin by NAA80 impacts cell migration.
    • 2018. Discovery of NAA80 as actin’s N-terminal acetyltransferase – a novel regulator of cytoskeleton dynamics.
    • 2018. Actin Acetylation.
    • 2016. Dynamic aspects of protein N-terminal acetylation in response to changes in nutrient availability.
    • 2015. Targeting of membrane proteins by means of N-terminal acetylation.
    • 2015. N-terminal acetylation meets the organelles.
    • 2015. Metabolic Regulation of Protein N-terminal Acetylation.
    • 2015. Evolutionary conservation of N-terminal acetyltransferase C (NatC) from yeast to human.
    • 2012. N-terminal acetyltransferase 30 (Naa30p/NatC) - Phenotypes of S. Cerevisiae naa30Δ strains.
    • 2012. ISOLATION OF SECRETED PROTEINS FROM YEAST AND MAMMALIAN CELL CULTURE.
    • 2012. GLUCOSE DEPENDENT DYNAMIC N-TERMINAL ACETYLATION IN SACCHAROMYCES CEREVISIAE.
    • 2012. Dynamicity and functional implications of N-terminal acetylation in S. cerevisiae.
    • 2012. Depletion of the N-terminal acetyltransferase hNaa30p disrupts Golgi integrity.
    • 2009. Time-lapse imaging of Arc protein degradation and synthesis in hippocampal neurons.
    Academic literature review
    • 2019. Co-translational, post-translational, and non-catalytic roles of N-terminal acetyltransferases. 1097-1114.
    • 2016. First things first: Vital protein marks by N-terminal acetyltransferases. 746-760.
    • 2015. (Hyper)tension release by N-terminal acetylation. 422-424.

    More information in national current research information system (CRIStin)

    PEER-REVIEWED SCIENTIFIC PUBLICATIONS (PubMed)

    Efficient and crucial quality control of HAP1 cell ploidy status.

    Beigl TB, Kjosås I, Seljeseth E, Glomnes N, Aksnes H*.

    Biol Open. 2020 Nov 12;9(11):bio057174. doi: 10.1242/bio.057174. PMID: 33184093

    *Corresponding authorship

     

    Exploiting the potential of commercial digital holographic microscopy by combining it with 3D matrix cell culture assays

    Hellesvik M, Øye H, Aksnes H*

    Sci Rep. 2020 Sep 7;10(1):14680. doi: 10.1038/s41598-020-71538-1.PMID: 32895419 

    *Corresponding authorship

     

    N-terminal acetylation of actin by NAA80 is essential for structural integrity of the Golgi apparatus

    Beigl TB, Hellesvik M, Saraste J, Arnesen T, Aksnes H*. 

    Exp Cell Res. 2020 May 15;390(2):111961. doi: 10.1016/j.yexcr.2020.111961. Epub 2020 Mar 21.PMID: 32209306 

    *Corresponding authorship

     

    Co-translational, Post-translational, and Non-catalytic Roles of N-Terminal Acetyltransferases

    Aksnes H*, Ree R, Arnesen T*.

    Mol Cell. 2019 Mar 21;73(6):1097-1114. Review. PMID: 30878283

    *Corresponding authorship

     

    Actin polymerization and cell motility are affected by NAA80-mediated posttranslational N-terminal acetylation of actin

    Aksnes H*, Marie M, Arnesen T, Drazic A.

    Commun Integr Biol. 2018 Oct 21;11(4):e1526572. PMID: 30534344

    *Corresponding authorship

     

    N-terminal Acetylation Levels Are Maintained During Acetyl-CoA Deficiency in Saccharomyces cerevisiae

    Varland S, Aksnes H, Kryuchkov F, Impens F, Van Haver D, Jonckheere V, Ziegler M, Gevaert K, Van Damme P, Arnesen T.

    Mol Cell Proteomics. 2018 Dec;17(12):2309-2323. PMID: 30150368

     

    NAA80 is actin's N-terminal acetyltransferase and regulates cytoskeleton assembly and cell motility

    Drazic A#Aksnes H#, Marie M#, Boczkowska M, Varland S, Timmerman E, Foyn H, Glomnes N, Rebowski G, Impens F, Gevaert K, Dominguez R, Arnesen T.

    Proc Natl Acad Sci U S A. 2018 Apr 24;115(17):4399-4404. PMID: 29581253

    # Shared first authorship

    Best paper of the year, Faculty of Medicine, UiB

    Received attention:

    From the cover Proc Natl Acad Sci USA 2018; vol. 115 no. 17.

    Commented in: NATure of actin amino-terminal acetylation Proc Natl Acad Sci USA 115(17):4314-16.

    Commented in: Actin's N-terminal acetyltransferase uncovered Cytoskeleton 75(7):318-22.

     

    Molecular determinants of the N-terminal acetyltransferase Naa60 anchoring to the Golgi membrane

    Aksnes H, Goris M, Strømland Ø, Drazic A, Waheed Q, Reuter N, Arnesen T.

    J Biol Chem. 2017 Apr 21;292(16):6821-6837. PMID: 28196861

     

    Microscopy-based Saccharomyces cerevisiae complementation model reveals functional conservation and redundancy of N-terminal acetyltransferases

    Osberg C, Aksnes H, Ninzima S, Marie M, Arnesen T.

    Sci Rep. 2016 Aug 24;6:31627. PMID: 27555049

     

    First Things First: Vital Protein Marks by N-Terminal Acetyltransferases

    Aksnes H, Drazic A, Marie M, Arnesen T.

    Trends Biochem Sci. 2016 Sep;41(9):746-760. Review. PMID: 27498224

     

    Holding it together: Naa60 at the Golgi

    Aksnes H, Marie M, Arnesen T.

    Oncotarget. 2015 Jun 30;6(18):15726-7. PMID: 26164078

     

    (Hyper)tension release by N-terminal acetylation

    Aksnes H, Drazic A, Arnesen T.

    Trends Biochem Sci. 2015 Aug;40(8):422-4. PMID: 26027460

     

    Molecular, cellular, and physiological significance of N-terminal acetylation

    Aksnes H, Hole K, Arnesen T.

    Int Rev Cell Mol Biol. 2015;316:267-305. Review. PMID: 25805127

     

    An organellar Nα-acetyltransferase, Naa60, acetylates cytosolic N termini of transmembrane proteins and maintains Golgi integrity

    Aksnes H, Van Damme P, Goris M, Starheim KK, Marie M, Støve SI, Hoel C, Kalvik TV, Hole K, Glomnes N, Furnes C, Ljostveit S, Ziegler M, Niere M, Gevaert K, Arnesen T.

    Cell Rep. 2015 Mar 3;10(8):1362-74. PMID: 25732826

    Best paper of the year, Dept. of Molecular Biology, UiB

     

    N-terminal acetylation by NatC is not a general determinant for substrate subcellular localization in Saccharomyces cerevisiae.

    Aksnes H, Osberg C, Arnesen T.

    PLoS One. 2013 Apr 15;8(4):e61012. doi: 10.1371/journal.pone.0061012. Print 2013.

    PMID: 23613772 

     

    The human N-alpha-acetyltransferase 40 (hNaa40p/hNatD) is conserved from yeast and N-terminally acetylates histones H2A and H4.

    Hole K, Van Damme P, Dalva M, Aksnes H, Glomnes N, Varhaug JE, Lillehaug JR, Gevaert K, Arnesen T.

    PLoS One. 2011;6(9):e24713. doi: 10.1371/journal.pone.0024713. Epub 2011 Sep 15.

    PMID: 21935442 

     

    All peer-reviewed publications in the database PubMed

    Henriette Aksnes - PubMed

    MY RESEARCH IS SUPPORTED BY FUNDING FROM:

    2020 -     Familien Blix' fond til fremme av medisinsk forskning

    2020 -     Konsul Søren Falch og Øyenlege Sigurd Falchs Fond for Medisinsk Vitenskap Falch Junior award

    2020 -     EPICS-XS (The European Proteomics Infrastructure Consortium)

    2020 -     Astri and Edvard Riisøens legat til fremme av vitenskapelig forskning

    2019 -     UiB, MedFak - Research/networking/portfolio activities

    2019 -     UiB - Funds awarded as part of being selected for the Momentum career development programme for early stage researchers

     

    THROUGH PROF. THOMAS ARNESEN'S PROJECTS MY WORK IS ALSO SUPPORTED BY:

    The European Research Council (ERC)

    The Research Council of Norway (RCN / NFR)

    The Norwegian Cancer Society (NCS)

    Helse Vest (HV)