Dr Jonathan W. Mueller PhD DSc

Dr Jonathan W. Mueller

Institute of Metabolism and Systems Research
Lecturer in Endocrine Biochemistry

Contact details

Address
Institute of Metabolism and Systems Research
College of Medical and Dental Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

Dr Mueller is interested in enzyme-catalysed reactions that modulate hormone function and act as biological switches. One of these transformations is the dynamic sulfation and de-sulfation of steroid hormones. Jon studies these sulfation pathways intensively, using a variety of biochemical, bioanalytical and cell biological techniques.

Dr Mueller has authored more than 25 primary research and review papers. His lab received funding from the European Commission (Marie Curie fellowship SUPA-HD 625451 and Erasmus actions), the Wellcome Trust (ISSF) and the MRC (Proximity-to-Discovery).

Jon is involved in various formats of outreach. He runs the biannual SUPA conference series on sulfation pathways – the last one took place in Germany in April 2019. Further outreach include the university’s Masterclasses programme for A level students, Marie Curie outreach and training events as well as gender and diversity presentations.

In collaboration with a Birmingham-based artist, Jon created journal cover art and presented this project at the university’s Worlds collide seminar series. Jon also presented private artwork at the Barber Institute of Fine Art at Recovery Art exhibitions.

Qualifications

  • Fellow of the Higher Education Academy, 2019
  • Distinguished visiting fellow at the Krupp Institute for Advanced Studies, Greifswald, Germany, 2015
  • Habilitation (DSc equivalent) in Biochemistry and Molecular Biology, University of Duisburg and Essen, Germany, 2012
  • PhD in Biochemistry, University of Halle and Wittenberg, Germany, 2004
  • Biochemistry diploma (MA equivalent, With Honours), University of Halle and Wittenberg, Germany, 2001

Biography

A protein biochemist by training, Dr Mueller earned his PhD at Max Planck Institute Dortmund working with Peter Bayer. With Peter, he then moved for post-doctoral and senior post-doc experience to the University of Duisburg and Essen.

Jon’s interest in sulfation pathways was sparked by two EMBO visiting research fellowships with Annalisa Pastore at the MRC National Institute for Medical Research in London, which is now part of the Crick Research Institute.

In 2012, Jon moved to Birmingham as a Marie Curie Senior Research Fellow to work on the sulfation of steroid hormones with Professor Wiebke Arlt. There, Jon now is Lecturer in Endocrine Biochemistry at the Institute of Metabolism and Systems Research. 

Teaching

1st medical year – pharmacology lectures within the Cell biology–Endocrinology–Pharmacology (CEP) module

Small group training in various aspects of Molecular Endocrinology for medical, biomedical and dental students

NMR "Basic Training" in Metabolomics - Compartmentalisation of Metabolism, University of Birmingham

Various training sessions on Marie Curie fellowships at UoB and at gender and career issues externally

Masterclass “Interested in the Biochemistry of Life?” for A level students, University of Birmingham

“Sulfation Pathways in Health & Disease” lecture for intercalating medical students

Research Tasters for medical and biomedical students

Postgraduate supervision

Dr Mueller welcomes diversity in his group. We are always interested in getting in touch with young scientists who are interested in our research. Please get in touch if you plan a lab placement or like to join the lab as a PhD or a postdoc.

Research

Our research into sulfation pathways is strongly informed by studying patients with genetic defects in different components of the sulfation machinery. In this way we realised that loss-of-function of the sulfation enzyme PAPSS2 cannot be compensated by the related enzyme PAPSS1 (JCEM 2015; 100(4): E672-80). Recently we could provide a molecular explanation for this finding: We reported a novel protein interaction between PAPSS2 and the sulfotransferase SULT2A1 (Mueller et al, JBC 2018; 293(25): 9724-35). On these grounds, we postulate that sulfate activation by PAPS synthases is an additional layer of regulation in sulfation pathways.

PAPS synthases have been our research focus for many years. Ground-breaking work was our first biophysical characterisation of these enzymes (JBC 2012; 287(21): 17645-55) that identified PAPSS2 as marginally stable protein. We have reviewed recent concepts of protein stability in light of these findings (doi: 10.3389/fmolb.2019.00031). It will be exciting to see how the stability of this important protein is changed, when studied within the living cell.

Structure and function of sulfation enzymes not only from humans, but also from other organisms are of interest to the group. Here, we contributed to a study analysing the redox regulation of the plant PAP phosphatase Sal1 (PNAS 2016; 113(31): E4567-76) and the structural elucidation of the plant sulfotransferase SOT18 (Sci Rep. 2017; 7(1): 4160). Clear evidence how insightful it can be to “look over the fence” of one’s own speciality.

Other activities

External positions of responsibility

Board member at the Canadian Institutes for Health Research Catalyst Grant: Sex as a Variable in Biomedical Research, Ottawa, Canada, 2017/2018

Referee for the European Union Marie Skłodowska Curie individual fellowships, since 2017

Member of the joint Editorial Board of the Journal of Molecular Endocrinology and Journal of Endocrinology, since 2018

Referee and guest editor of various scientific journals

Conference organisation

SUPA 2019 conference – 11–12 April, Rauischholzhausen Castle, Germany

SUPA 2017 conference – 23–25 April, Birmingham, UK

SUPA 2015 conference – 28–30 September, Greifswald, Germany

S•Bio 2017 Conference on Plant & Human Sulfur Biology, 10–14 September, Lake Balaton, Hungary

S•Bio 2020 Conference on Plant & Human Sulfur Biology, 21–24 September, Norwich, UK 

Publications

Mueller JW, Foster PA (2018) Steroid sulfation research has come a long way. Editorial. J Mol Endocrinol. 61(2):E5-E6

Foster PA, Mueller JW (2018) SULFATION PATHWAYS: Insights into steroid sulfation and desulfation pathways. Review. J Mol Endocrinol. 61(2):T271-83

Mueller JW, Idkowiak J, Gesteira TF, Vallet C, Hardman R, van den Boom J, Dhir V, Knauer SK, Rosta E, Arlt W (2018) Human DHEA sulfation requires direct interaction between PAPS synthase 2 and DHEA sulfotransferase SULT2A1. J Biol Chem. 293(25):9724-35

Chan KX, Mabbitt PD, Phua SY, Mueller JW, Nisar N, Gigolashvili T, Stroeher E, Grassl J, Arlt W, Estavillo GM, Jackson CJ, Pogson BJ (2016) Sensing and signaling of oxidative stress in chloroplasts by inactivation of the SAL1 phosphoadenosine phosphatase. Proc Natl Acad Sci U S A. 113(31):E4567-76

Mueller JW, Gilligan LC, Idkowiak J, Arlt W, Foster PA (2015) The Regulation of Steroid Action by Sulfation and Desulfation. Review. Endocr Rev. 36(5):526-63

Oostdijk W, Idkowiak J, Mueller JW, House PJ, Taylor AE, O'Reilly MW, Hughes BA, de Vries MC, Kant SG, Santen GW, Verkerk AJ, Uitterlinden AG, Wit JM, Losekoot M, Arlt W (2015) PAPSS2 deficiency causes androgen excess via impaired DHEA sulfation--in vitro and in vivo studies in a family harboring two novel PAPSS2 mutations. J Clin Endocrinol Metab. 100(4):E672-80

van den Boom J, Heider D, Martin SR, Pastore A, and Mueller JW (2012) PAPS synthases, naturally fragile enzymes specifically stabilized by nucleotide binding. J Biol Chem. 287(21):17645-55

Mueller JW, Link NM, Matena A, Hoppstock L, Rüppel A, Bayer P, Blankenfeldt W (2011) Crystallographic proof for an extended hydrogen-bonding network in small prolyl isomerases. J Am Chem Soc. 133(50):20096-9

For a full list of Dr Mueller's publications.

View all publications in research portal