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Wittung-Stafshede's Protein Biophysics lab

We use biophysical methods to study (1) the role of cell-like conditions on protein chemistry, (2) copper-transport mechanisms in human cells and (3) protein misfolding, and its tuning, in Parkinson's disease.

Applications by exceptional students for postdoctoral fellowships will always be considered. If so send email to Pernilla.

The question of how a protein is formed is one of life's great mysteries.The understanding of protein folding and misfolding processes, and how external factors affect these reactions, are critical for finding rational treatment of many debilitating conditions like Alzheimer´s and Parkinson's disease, type II diabetes, prion diseases, and Menke's and Wilson's diseases. Knowledge about protein folding is also crucial in protein design and protein-structure prediction efforts. The projects in my lab focus on fundamental aspects of protein folding reactions using model systems as well as on specific human proteins involved in key metabolic pathways.

One branch of my research aims to increase our fundamental knowledge of how proteins fold and misfold in vitro and in vivo. The major focus of this part has for a long time been on two key classes of proteins: metal-binding and oligomeric proteins. Folding of these proteins does not only involve polypeptide folding, but also inter-protein interactions and thus their folding pathways may be affected by metal interactions and protein-protein interactions, respectively. To mimic the crowded cellular environment, experiments are performed in the presence of crowding agents. Recent efforts in terms of folding relate directly to protein misfolding and human diseases, with special emphasis on human (alpha-synuclein) and bacterial (curli) amyloid proteins and the use of small synthetic molecules to tune the reactions in desired ways. The other branch of my research aims to understand the mechanisms of proteins involved in cellular copper transport. Copper is an essential metal in many enzymes but since free copper ions can be toxic, copper transport is regulated. We focus on proteins in the secretory pathway, searching for thermodynamic, mechanistic and kinetic parameters for how the copper chaperone Atox1 delivers copper to metal-binding domains in the Wilson disease protein and what role intra-protein domain-domain interactions play. To characterize reactions of target proteins, biophysical and biochemical techniques (spectroscopy, calorimetry, NMR, X-ray, SPR, stopped-flow, AFM, EM etc.) are combined with strategic protein mutagenesis and theoretical approaches, and sometimes in vivo experiments.

NEWS

Maria and Alexander defended their PhD theses in October and December 2013. Maria has left for a postdoc at University of Oxford!

New groupmembers have arrived in spring 2014: Anna and Svenja on short projects, Tanumoy and Sandeep for 2 years.

Pictures from lab bowling event in May 2014:

Instrumentation in the lab
Chirascan stopped-flow mixer (with CD, fluorescence and absorption detection)
Fluorometer
ITC and DSC micro-calorimeters
Circular dichroism spectropolarimeter
Biacore
AKTA purifiers
polarimeter

Lab members
Moritz Muller (grad student, Sept 2009-), Jörgen Åden (research engineer, Sep 2011-), Erik Chorell (researcher, May 2012-), Dana Kahra (postdoc fellow, Feb 2013-), Anna Götheson (exam project, April-May 2014), Svenja Petzoldt (undergraduate project, April-August 2014), Sandeep Sharma (researcher, April 2014-), Tanumoy Mondol (postdoc fellow, May 2014-)
 

 

Previous group members:
Alexander Christiansen (PhD 2013, Chemistry, Umeå),  Maria Palm-Espling (2013 PhD, Chemistry, Umeå), Ximena Aguilar (grad student, Sept 2009-sept 2012), Christoph Weise (research engineer Umeå, Sep 2011-July 2012), Istvan Horvath (Postdoc fellow Umeå, Feb 2010-July 2012), Erik Rosenbaum (research assistant Umeå, 6 months 2011), Irina Pozdnyakova (Postdoc fellow Umeå, Oct 2008-Oct 2010), Hamidur Rahaman (Postdoc fellow Umeå, Feb 2009-Jan 2010), Agustina Rodriguez-Granillo (2009 PhD, Biochemistry, Rice) Loren Stagg (2009 PhD, Biochemistry, Rice), Faiza Hussain (2009 PhD, Biochemistry, Rice), Erik Sedlak (Post-doctoral fellow, 2007-2008), Michael Perham (2008 PhD Chemistry, Rice), Julie Liao (undergraduate student, 2004-2007; Honors thesis 2007), Kathryn Luke (2007 PhD, Biochemistry, Rice), Corey Wilson (2005 PhD, Biochemistry, Rice, co-advisor), David Apiyo (Post-doctoral fellow, 2005-2006), Christopher Brown (laboratory technician, 2004-2005), B.K. Muralidhara (Post-doctoral fellow, 2002-2004), Jesse Guidry (laboratory technician, 1999-2003), Catherine Higgins (2004 PhD, Chemistry, Tulane), Kathryn Jones (2003 PhD, Molecular and Cellular Biology Graduate Program, Tulane), Susanne Griffin and Andrea Vitello  (undergraduate students 2000-2003; Honors theses 2003), David Apiyo (2003 PhD, Chemistry, Tulane), Irina Pozdnyakova (Post-doctoral fellow, 2002-2003), Irina Pozdnyakova (2002 PhD, Chemistry, Tulane), Johan Kajanus (1994 M.Sc,, Chalmers, Sweden), Malin Ardhammar (1996 M.Sc., Chalmers, Sweden), Michael Suh (1998 Summer Undergraduate Research Program (SURF), Caltech, LA)

Funding
Swedish Research Council, Wallenberg Scholar, Göran Gustafsson
 

Contact Information                                                             

Pernilla Wittung-Stafshede
Professor, Chemistry Department
Umeå University
901 87 Umeå, Sweden
pernilla.wittung@chem.umu.se
office phone: +46-90-786 5347
lab phone: +46-90-786 5268

Publikationer

Författare

Titel

År sorteringsordning

Fulltext

Mondol, Tanumoy
Ådén, Jörgen
Wittung-Stafshede, Pernilla

Copper binding triggers compaction in N-terminal tail of human copper pump ATP7B
Biochemical and Biophysical Research Communications - BBRC, 470(3): 663-669

2016

-

Kahra, Dana
Kovermann, Michael
Wittung-Stafshede, Pernilla

The C-Terminus of Human Copper Importer Ctr1 Acts as a Binding Site and Transfers Copper to Atox1
Biophysical Journal, 110(1): 95-102

2016

-

Öhrvik, Helena
Wittung-Stafshede, Pernilla

Identification of New Potential Interaction Partners for Human Cytoplasmic Copper Chaperone Atox1: Roles in Gene Regulation?
International Journal of Molecular Sciences, 16(8): 16728-16739

2015

-

Chermenina, Maria
Chorell, Erik
Pokrzywa, Malgorzata; et al.

Single injection of small-molecule amyloid accelerator results in cell death of nigral dopamine neurons in mice
Parkinson's Disease, 1

2015

Hämta

Perdersen, Martin Nors
Fodera, Vito
Horvath, Istvan; et al.

Direct Correlation Between Ligand-Induced alpha-Synuclein Oligomers and Amyloid-like Fibril Growth
Scientific Reports, 5

2015

Hämta

Chorell, Erik
Andersson, Emma
Evans, Margery L.; et al.

Bacterial Chaperones CsgE and CsgC Differentially Modulate Human α-Synuclein Amyloid Formation via Transient Contacts
PLoS ONE, 10(10): 1-11

2015

Hämta

Sharma, Sandeep K.
Chorell, Erik
Wittung-Stafshede, Pernilla

Insulin-degrading enzyme is activated by the C-terminus of alpha-synuclein
Biochemical and Biophysical Research Communications - BBRC, 466(2): 192-195

2015

-

Sharma, Sandeep K
Chorell, Erik
Steneberg, Pär; et al.

Insulin-degrading enzyme prevents alpha-synuclein fibril formation in a nonproteolytical manner
Scientific Reports, 5

2015

Hämta

Wittung-Stafshede, Pernilla

Tuning of Alpha-Synuclein Aggregation by Small Molecules and Bacterial Proteins
Biophysical Journal, 108(2): 522A-522A

2015

-

Singh, Pardeep
Chorell, Erik
Krishnan, K Syam; et al.

Synthesis of multiring fused 2‑pyridones via a nitrene insertion reaction: fluorescent modulators of α‑synuclein amyloid formation
Organic Letters, 17(24): 6194-6197

2015

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Sidansvarig: Pernilla Wittung-Stafshede
2014-05-19

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