Howard Jacobs

Professor of Molecular Biology, 1996 – 

Academy Professor 2006-2016

My research interests include mitochondria, mitochondrial disease and cellular energy metabolism.

My profile at researchportal.tuni.fi

Mitochondrial Biology research group

Coordinating and delivering Masters level courses in molecular biology 

Graduate training and supervision in molecular biology of mitochondria 

Research in mitochondrial biology 

Outreach: TV documentaries, public-access colloquia, cafe sci, city ambassador programme  

Editorial and support activities in scientific communication

Mitochondria; mitochondrial DNA; respiratory chain; mitochondrial disease; metabolism; Drosophila; DNA replication; nuceloids; RNA processing; protein synthesis; alternative respiratory chain enzymes

Positions 

Director, Institute of Biotechnology, University of Helsinki, 2015-2017 

Director, Academy of Finland Centre of Excellence FinMIT, 2002-2019 

Coordinator, EU projects MBDD (1994-1998), MitAGE (2001-2003), MitEURO (2002-2005) 

 

Awards 

2016 Life Sciences Film Festival, Prague, awards for TV science documentary series 'The Future of Finland'

2014 Finnish Cultural Foundation, National Science Prize 

2012 Finnish Cultural Foundation, Pirkanmaa Region Science Prize 

2009 Professor of the Year, Finnish Professors’ Union, ‘2009 

2007 Knight, First Class, of the Order of the White Rose of Finland 

2004 Descartes Prize – EU prize for outstanding trans-national research, Coordinator 

2002 Finnish Academy of Science and Letters, Foreign Member 

2001 EMBO Member 

 

Editor in Chief, Fly (2019 - )

Chief Editor, EMBO Reports, 2009-2014

EMBO Course and Meetings Committees, 2004-2010

Honorary Secretary, UK Genetics Society, 1996-2003

 

My group aims to develop fundamental knowledge useful for the design of novel therapies based upon nutritional, pharmaceutical and genetic approaches. Drosophila and mice models are used to evaluate nutritional effects, as well as to identify signaling pathways involved in mitochondrial stress responses, revealing new drug targets.

Mitochondrial DNA replication and disease

A variety of human diseases, ranging from devastating conditions of infancy through to degenerative disorders seen mainly in old age, are associated with genetic lesions of mitochondrial DNA. In order to understand how mtDNA maintenance shapes cell physiology, and elucidate how it can go wrong in disease and ageing, we are studying the fundamental mechanisms of DNA replication in model organisms, using a combination of genetic and biochemical approaches.

Nuclear-mitochondrial interactions in Drosophila

We use various Drosophila mutants with defects in mitochondrial function to analyse the contributions of nuclear and mitochondrial genotype, as well as environmental factors such as diet and exposure to antibiotics, to organismal phenotype. Much of our attention has been focusSed on the tko25t strain, which carries a point mutation in the gene for mitoribosomal protein S12, and is a useful model for studying human mitochondrial disease. We are also studying the roles in animal development of global regulators of mitochondrial function, and the physiological effects of respiratory chain dysfunction in the nervous system, using flies as a model system.

Alternative respiratory chain enzymes: a possible therapy for mitochondrial disorders?

The genomes of plants, fungi and many microbes, as well as some primitive animal phyla, contain genes for alternative mitochondrial respiratory chain enzymes, which buffer a host of redox and bioenergetic stresses similar to those encountered in humans under pathological conditions. The genes for these alternative enzymes are absent from humans and other complex animals. However, we reasoned that their introduction may alleviate many of the physiological defects associated with mitochondrial disease. We have transferred the relevant genes from the tunicate Ciona, as well as from fungi, into human cells and model organisms, creating proof of concept for such protection. Our current research focuses on ascertaining the potential of these enzymes in therapy, both by exploring what specific pathologies they can prevent, as well as testing out ways to safely introduce them in a therapeutically effective form to humans. In addition we are studying the natural biology of the alternative enzymes in Ciona, to understand better how they can be most effectively used in humans.

 

Faculty of Medicine and Health Technology – BioMediTech unit

Molecular biology; genetics; biochemistry; cell biology

~15,1 M€ (Academy of Finland, European Research Council, EU, Sigrid Juselius Foundation )

2015-2017 Director, Institute of Biotechnology, University of Helsinki 

2006-2016 Academy Professor, University of Tampere 

1996- Professor of Molecular Biology, University of Tampere

1984-94 Royal Society Research Fellow & Reader in Genetics, University of Glasgow, Scotland 

1981-1983 NATO/SRC Postdoctoral Fellow, California Institute of Technology, USA 

  

PhD (1981) University of Glasgow (Beatson Institute, Lady Tata Memorial Scholar), Molecular Biology 

MA (1981) University of Cambridge 

BA (1977) University of Cambridge, (St John's College: Whytehead Scholar) 

Terzioglu M, Veeroja K, Montonen T, Ihalainen TO, Salminen TS, Bénit P, Rustin P, Chang Y-T, Nagai T, Jacobs HT (2023) Mitochondrial temperature homeostasis resists external metabolic stresses. eLife. (under revision). bioRxiv, doi: 10.1101/2023.05.24.542069 

Jacobs HT, Szibor M, Rathkolb B, da Silva-Buttkus P, Aguilar-Pimentel JA, Amarie OV, Becker L, Calzada-Wack J, Dragano N, Garrett L, Gerlini R, Hölter SM, Klein-Rodewald T, Kraiger M, Leuchtenberger S, Marschall S, Östereicher MA, Pfannes K, Sanz-Moreno A, Seisenberger C, Spielmann N, Stoeger C, Wurst W, Fuchs H, Hrabě de Angelis M, Gailus-Durner V (2023) AOX delays the onset of the lethal phenotype in a mouse model of Uqcrh (complex III) disease. Biochim Biophys. Acta Mol. Basis Dis. 1869, 166760. doi: 10.1016/j.bbadis.2023.166760

Jacobs HT, Tuomela T, Lillsunde P (2023) Nuclear genetic background influences the phenotype of the Drosophila tko25t mitochondrial protein-synthesis mutant. G3 (Bethesda) 13, jkad078. doi: 10.1093/g3journal/jkad078, ‘June Featured Article’.

Jacobs HT, Ballard JWO (2022) What physiological role(s) does the Alternative Oxidase play in animals? Biochim. Biophys. Acta Bioenerget. 1863, 148556 doi: 10.1016/j.bbabio.2022.148556

Billingham L, Stoolman J, Vasan K, Rodriguez A, Poor T, Szibor M. Jacobs HT, Reczek C, Miska J, Rashid A, Chandel N (2022) Mitochondrial electron transport chain is necessary for NLRP3 inflammasome activation. Nat. Immunol. 23, 692–704. doi: 10.1038/s41590-022-01185-3,

Giordano L, Aneja MK, Sommer N, Alebrahimdehkordi N, Weissmann N, Rudolph C, Plank C, Jacobs HT, Szibor M (2021) Alternative oxidase encoded by sequence-optimized and chemically-modified RNA transfected into mammalian cells is catalytically active. Gene Ther. 29, 655-664 .doi: 10.1038/s41434-021-00235-z

Bremer K, Yasuo H, Debes PV, Jacobs HT (2021) The alternative oxidase (AOX) increases sulphide tolerance in the highly invasive marine invertebrate Ciona intestinalis, J. Exp. Biol. 224, jeb242985. doi: 10.1242/jeb.242985 [editor’s commentary at https://doi.org/10.1242/jeb.243318]

González de Cózar JM, Carretero-Junquera M, Ciesielski GL, Miettinen SN, Varjosalo M, Kaguni, LS, Dufour E, Jacobs HT (2020) A second hybrid-binding domain modulates the activity of Drosophila ribonuclease H1. J. Biochem. 168, 515-533. 

Yalgin C, Rovenko B, Andjelković A, Neefjes M, Oymak B, Dufour E, Hietakangas V, Jacobs HT (2020) Effects on dopaminergic neurons are secondary in COX-deficient locomotor dysfunction in Drosophila. iScience 23, 101362.

Sommer N, Pak O, Alebrahimdehkordi N, Knoepp F, Strielkov I, Scheibe S, Dufour E, Andjelković A, Sydykov A, Saraji A, Petrovic A, Quanz K, Hecker M, Kumar M, Wahl J, Kraut S, Seeger W, Schermuly R, Ghofrani HA, Ramser K, Braun T, Jacobs HT, Weissmann N, Szibor M (2020) Bypassing mitochondrial complex III using alternative oxidase inhibits acute pulmonary oxygen sensing. Sci. Adv. Sci. Adv. 6, eaba0694.

Bahhir D, Yalgin C, Ots L, Järvinen S, George J, Naudi A, Krama T, Krams I, Tamm M, Andjelković A, Dufour E, González de Cózar J, Gerards M, Parhiala M, Pamplona R, Jacobs HT, Jõers P (2019) mtDNA stress reprograms metabolism via cytonuclear protein modifications and Akt deactivation. PLoS Genetics 15, e1008410.  

Salminen TS, Cannino G, Oliveira MT, Lillsunde P, Jacobs HT, Kaguni LS (2019) Lethal interaction of nuclear and mitochondrial genotypes in Drosophila melanogaster. G3 9, 2229-2234. (F1000prime selected artcile) 

Andjelković A, Mordas A, Bruisma L, Ketola A, Cannino G, Giordano L, Dhandapani PK, Szibor M, Dufour E, Jacobs HT (2018) Expression of the alternative oxidase influences JNK signalling and cell migration. Mol. Cell. Biol. 38, e00110-18. 

Dogan SA, Cerutti R, Benincá C, Brea-Calvo G, Jacobs HT, Zeviani M, Szibor M, Viscomi C (2018) Perturbed redox signaling exacerbates a mitochondrial myopathy. Cell Metab. 28, 764-775. 

Toompuu M, Tuomela T, Laine PK, Paulin L, Dufour E, Jacobs HT (2018) Polyadenylation and degradation of structurally abnormal mitochondrial tRNAs in human cells. Nucl. Acids Res. 46, 5209-5226 

Gerards M, Cannino G, González de Cózar JM, Jacobs HT (2018) Intracellular vesicle trafficking plays an essential role in mitochondrial quality control. Mol. Biol. Cell 29, 809-819. 

Chrétien D, Bénit P, Ha H-H, Keipert S, El-Khoury R, Chang Y-T, Jastroch M, Jacobs HT, Rustin P, Rak M (2018) Mitochondria are maintained physiologically at close to 50 ºC. PLoS Biol. 16, e2003992. 

Mills EL, Kelly B, Logan A, Cosfsta AS, Varma M, Bryant CE, Tourlomousis P, Däbritz JH, Gottlieb E, Latorre I, Corr SC, McManus G, Ryan D, Jacobs HT, Szibor M, Xavier RJ, Braun T, Frezza C, Murphy MP, O'Neill LA (2016) Succinate Dehydrogenase supports metabolic repurposing of mitochondria to drive inflammatory macrophages. Cell 167, 457-470. 

El-Khoury R, Kaulio E, Lassila KA, Crowther DC, Jacobs HT, Rustin P (2016) Expression of the alternative oxidase mitigates beta-amyloid production and toxicity in model systems Free Rad. Biol. Med. 96, 57-66.