| Seyedarabi, Arefeh |
Assistant Professor of Biochemistry and Structural Biology
Tel: +98-21 66956974
Research in this laboratory focuses on the structure and function of proteins in health and disease using the necessary techniques and tools including, at present, protein biochemical and biophysical characterisation, structural determination and bioinformatics analyses. The major structural technique used is X-ray crystallography to solve novel structures both in their Apo or Halo forms. The research areas in this laboratory mainly takes inspiration from nature and also the valuable knowledge of Traditional Iranian Medicine (TIM) or Persian Medicine which is geographically most accessible and easily at hand. Current ongoing research is on the structural determination of sturgeon fish hemoglobin from the Caspian Sea which is of great novelty and native to the region. The use of TIM recommended flower extracts and the available knowledge of their active constituents is used in another research project in the prevention of amyloid formation aimed at neurodegenerative diseases, in particular Alzheimer's disease. Other upcoming research projects involve aromatherapy and ozone therapy. Additionally, optimisation of crystallisation is another research area for which I strive for as it is an expertise close to my heart.
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Name: Arefeh Seyedarabi
Appointment: Assistant Professor of Biochemistry and Structural Biology
Office Address: Institute of Biochemistry and Biophysics,
University of Tehran P.O.Box 13145-1384 Tehran, Iran
Telephone No.: +98-21 66956974
Fax: 0098 21 66404680
March 2012-present: Assistant Professor of Biochemistry, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran
Structure-function studies of proteins involved in health and disease using various biochemical and biophysical techniques.
Jan 2011-2012: Senior Research Associate, Institute of Structural and Molecular Biology, University College London (Funded by British Heart Foundation)
My second postdoctoral research associate position was with Dr Snezana Djordjevic working on the structural and functional analyses of neuropilin-1 and neuropilin-2 interactions with VEGF which involved thermodynamic and kinetics experiments, X-ray crystallography, cell-free and cell-based assays as well as in vivo studies.
May 2007- 2010: Postdoctoral Research Assistant, School of Biological and Chemical Sciences, Queen Mary University of London (in collaboration with University of Kent, UK and Funded by BBSRC)
My postdoctoral research assistant position was with Professor Richard Pickersgill studying the substrate recognition and reaction mechanism of methyltransferases from the cobalamin (Vitamin B12) biosynthetic pathway (in collaboration with Professor Martin Warren, University of Kent). I was able to solve the structures of the following methyltransferases; CobF, CobM and CobL (C- terminal domain) in complex with S-adenosyl homocysteine (the demethylated form of the methyl donor S- adenosyl methionine). I have a first author publication (in Acta Cryst F) and will have more publications pending on the results obtained from this study.
Oct. 2003- 2007: PhD in Structure-function studies of proteins involved in infection, School of Biological and Chemical Sciences, Queen Mary University of London (in collaboration with University of Tokyo, Tokyo, Japan)
The focus of my study was on proteins belonging to the human pathogenic bacteria Listeria
monocytogenes and in particular Shigella flexneri (in collaboration with Professor Chihiro Sasakawa, University of Tokyo) and also the plant pathogenic bacteria Bacillus subtilis. I solved the structure of the dimeric form of Shigella flexneri IpaH9.8 E3 ubiquitin ligase and showed for the first time that its human substrate is U2AF35. In the study of Bacillus subtilis, I solved a number of structures involving Michaelis complexes of pectate lyase bound to different polygalacturonates to unravel the reaction mechanism of the enzyme as well as carrying out ITC experiments to unravel the binding affinity and stoichiometry of hexagalacturonate and pectate lyase. I have first author publications in FEBS Letters and Biochemistry from the studies on Shigella flexneri IpaH9.8 and Bacillus subtilis pectate lyase, respectively.
Sept. 2000-June 2003: First Class Honours BSc degree in Genetics and Microbiology,School of Biological Sciences, Queen Mary University of London (obtained the Westfield Trust Prize for Outstanding Academic Achievement)
Laboratory/computer based Skills:
- Molecular Biology -all necessary skills to make constructs (including bicistronic constructs) and also site-directed mutagenesis. I have made many constructs to date using pGEM-T Easy, pET and pGex vectors.
- Protein biochemistry –covering protein over-production, purification, SDS-PAGE and native-PAGE analyses, affinity chromatography, ion exchange chromatography and gel filtration chromatography. I have experience in over-producing and purifying numerous difficult proteins by varying induction temperature, duration of induction and E. coli cell strains as well as investigating different buffer environments for proteins such as pH and salt concentration. I also have experience in over-producing soluble human protein in E. coli through gene sequence adaptation.
- Protein characterisation (functional, biophysical and structural) -use of bioinformatic tools (e.g. from Expasy and EBI websites), limited proteolysis, pull-down assays, ubiquitination assays, western blot analysis, gel filtration, co-expression, circular dichroism (CD), dynamic light scattering (DLS), isothermal titration calorimetry (ITC), Surface Plasmon Resonanace (Biacore), crystallisation screening, and X-ray crystallography (at various synchrotron sources; previously at SRS and presently at Diamond, ESRF and BSRF).
- Structure determination- I have experience preparing and freezing crystals, taking crystals to synchrotron sources, collecting datasets, solving and analysing structures using programs such as iMosflm, CCP4 based programs, CNS, Phenix, Coot and PyMoL. I have on many occasions collected native datasets as well as Single wavelength Anomalous Dispersion (SAD) or Multi-wavelength Anomalous Dispersion (MAD) datasets from Selenium labeled proteins and heavy metal soaked crystals.
- Bioinformatics analyses- use of necessary tools and software to analyse DNA/ protein sequences and protein structures, including those provided in Expasy, Ebi, NCBI webpages, as well as Phyre2, MEGA6, iToL, PhyoT, Chimera, LigPlot and PyMoL.
ISI journal/online Publications
1. Baharara J, Ramezani T, Divsalar A, Mousavi M and Seyedarabi A, 'Induction of apoptosis by geen synthsesized gold nanoparticles through activation of caspase-3 and 9 in human cervical cancer cells', Avicenna J Med Biotechnol, 8 (2): 75-83, 2016
2. Koohshekan B, Divsalar A, Saiedifar M, Saboury AA, Ghalandari B, Gholamian A and Seyedarabi A, 'Protective effects of aspirin on the function of bovine liver catalase: A spectroscopy and molecular docking study', Journal of Molecular Liquids, 218: 8-15, 2016
3. Bohlooli M, Moosavi-Movahedi AA, Taghavi F, Saboury AA, Maghami P, Seyedarabi A, Moosavi Movahedi F, Ahmad F, Shockravi A, Habibi-Rezaei M, 'Inhibition of fluorescent advanced glycation end products (AGEs) of human serum albumin upon incubation with 3-β-hydroxybutyrate', Mol Biol Rep, 41 (6): 3705-13, 2014
4. Divsalar A, Razmi M, Saboury AA, Seyedarabi A, 'The design and characterisation of a novel beta-casein-vehicle loaded with platinum anticancer drug for drug delivery', Anticancer Agents Med Chem, 14 (6): 892-900, 2014
5. Ahmadzade Kermani H, Shockravi A, Moosavi-Movahedi Z, Khalafi-Nezhad A, Behrouz S, Tsai Fu-Yuan, Hakimelahi G H, Seyedarabi A and Moosavi-Movahedi AA, 'A surfactant-heme-sulfonyl imidazole system as a nano-artificial enzyme', J IRAN CHEM SOC, 10: 961-968, 2013
6. Arefeh Seyedarabi, Lili Cheng, Ian Zachary and Snezana Djordjevic, ‘Production of soluble human vascular endothelial growth factor VEGF-A165-heparin binding domain in Escherichia coli ', PLOS ONE, 8 (2), e55690, 2013
7. Azadeh Hekmat, Ali A. Saboury, Adeleh Divsalar, Arefeh Seyedarabi, ‘Structural effects of TiO2 nanoparticles and doxorubicin on DNA and their antiproliferative roles on T47D and MCF7 cells', Anti Cancer Agents in Medicinal Chemistry, 13 (6): 932-51, 2013
8. Bohlooli M, Moosavi-Movahedi AA, Taghavi F, Habibi-Rezaei M, Seyedarabi A, Saboury AA, Ahmad F, 'Thermodynamics of molten globule state of human serum albumin by 3-β-hydroxybutyrate as a ketone body', Int J Biol Macromol, 54: 258-63, 2013
9. Evelyne Deery, Susanne Schroeder, Andrew D. Lawrence, Samantha L. Taylor, Arefeh Seyedarabi, Jitka Waterman, Keith S. Wilson, David Brown, Michael A. Geeves, Mark J. Howard, Richard W. Pickersgill and Martin J. Warren, 'An enzyme-trap approach allows isolation of intermediates in cobalamin biosynthesis', Nat Chem Biol, 8(11), 933-940, 2012
10. Adeleh Divsalar, Ali A. Saboury, Zohre Zare, Mohammad E. Kefayati, Arefeh Seyedarabi, ‘Characterization and side effect analysis of a newly designed nanoemulsion targeting human serum albumin for drug delivery', Colloids and Surface B: Biointerfaces, 98, 80-84, 2012
11. Adeleh Divsalar, Sajedeh E. Damavandi, Ali A. Saboury, Arefeh Seyedarabi and Ali A. Moosavi-Movahedi, ‘Calorimetric and Spectroscopic investigations οf β-lactoglobulin upon interaction with copper ion', Journal of dairy research, 79, 209-215, 2012
12. Arefeh Seyedarabi, A method for labeling polyacrylamide gels, Protocol Exchange, doi:10.1038/protex.2011.222, published online 24 March 2011
13. Arefeh Seyedarabi, Thomas Hutchison, Teng T. To, Evelyn Deery, Amanda Brindley, Martin J. Warren and Richard W. Pickersgill, 'Cloning, purification and preliminary crystallographic analysis of cobalamin methyltransferases from Rhodobacter capsulatus', Acta Cryst, F66, 1652-1656, 2010
14. Arefeh Seyedarabi, James A. Sullivan, Chihiro Sasakawa and Richard W. Pickersgill, ‘A disulfide driven domain swap switches off the activity of Shigella IpaH9.8 E3 ligase', FEBS letters, 584 (19), 4163-4168, 2010
15. Arefeh Seyedarabi, ‘The orchestrators of Shigella flexneri infection', Crystallography Reviews, 16 (2), 145-165, 2010
16. Arefeh Seyedarabi, Teng T. To, Salyha Ali, Syeed Hussain, Markus Fries, Robert Madsen, Mads H. Clausen, Susana Teixteira, Keith Brocklehurst and Richard W. Pickersgill, ‘Structural and thermodynamic insights into substrate specificity and the anti β-elimination mechanism of pectate lyase', Biochemistry, 49 (3), 539-546, 2010
17. Dana Heldt, Stefanie Frank, Arefeh Seyedarabi, Dimitrios Ladakis, Joshua B.Parsons, Martin J. Warren, Richard W. Pickersgill, ‘Structure of a trimeric bacterial microcompartment shell protein, EtuB, associated with ethanol utilisation in Clostridium kluyveri', Biochemical Journal, 423, 199-207, 2009
18. Amy Ooi, Syeed Hussain, Arefeh Seyedarabi, and Richard W. Pickersgill, ‘Structure of internalin C from Listeria monocytogenes', Acta Cryst D, D62, 1287-1293, 2006
19. Jun Okuda, Takahito Toyotome, Naoyuki Kataoka, Mutsuhito Ohno, Hiroyuki Abe, Yoshiro Shimura, Arefeh Seyedarabi, Richard W. Pickersgill, Chihiro Sasakawa, ‘Shigella effector IpaH9.8 binds to a splicing factor U2AF35 to modulate host immune responses', Biochemical and Biophysical Research Communications, 333, 531-539, 2005
A. Seyedarabi, T. Hutchinson, M. J. Warren and R. W. Pickersgill, ‘The Methyltransferases of cobalamin (vitamin B12) biosynthesis', poster presented at the Young Crystallographers Satellite meeting and the main British Crystallographic Association Spring meeting, April 2009, Loughborough University (was awarded the David Blow poster prize)
A. Seyedarabi and R. W. Pickersgill, ‘Pectate lyase, a key enzyme in phytopathogenesis', poster presented at the Biological Structures group Winter meeting on ‘Structural Biology of Pathogens', 18th December 2006, University of Birmingham
A. Seyedarabi, S. Hussain, M, Fries, K. Brocklehurst and R. W. Pickersgill, ‘Mechanism of Bacillus subtilis pectate lyase', poster presented at the Biological Structures Group Winter meeting on ‘Structural enzymology', 19th December 2005, University of Bristol
A. Seyedarabi, Chihiro Sasakawa and R.W. Pickersgill, ‘Protein-protein interaction essential for Shigella flexneri infection', poster presentation, 12th-14th April 2005, Loughborough University
A. Seyedarabi and R.W. Pickersgill, ‘Characterisation of protein-protein interactions in Shigella infection: IpaH9.8 interferes with U2AF35-dependent pre-mRNA splicing', poster presented at 2nd year PhD Poster presentation session, February 2005, Queen Mary University of London
Crystal structure determination of hemoglobin from two sturgeon species of fish, Acipenser persicus and Acipenser stellatus', 13th Conference on Biological Chemistry (CBC), 2015, Ardabil, Iran
‘Structure-function studies of three types of enzymes involved in disease; a pectate lyase, an E3 ubiquitin ligase and three methyltransferases', International Conference on Biophysical Chemistry (ICBC), May 2012, Ardabil, Iran
‘Structural, Functional and Thermodynamic Analyses of Neuropilin-VEGF HeparinInteractions', Institute of Structural & Molecular Biology Retreat meeting, June 2011, Robinson College, Cambridge, UK
‘Vitamin B12 and the seven methyltransferase domains', Tetrapyrrole Discussion Group meeting, 8th April 2010, Royal College of Pathologists, London, UK
‘Structural and functional studies of IpaH9.8 from Shigella flexneri', Winter Biological Structures Group Meeting, December 2009, Royal Free Hospital, London, UK
‘Domain swapping in S. flexneri IpaH9.8', Young Crystallographers Satellite meeting, April 2009, Loughborough University, Loughborough, UK
‘Structural studies of the methyltransferases involved in cobalamin (vitamin B12) biosynthesis', Tetrapyrrole Discussion Group meeting, 1st April 2008, The Novartis Foundation, London, UK
‘Pectate lyase- structural and thermodynamic studies', 18th December 2007, Collaborative meeting on the bacterial Type II secretion system, Lyon, France
‘A recipe for binding and catalysis by pectate lyase', 16th April 2007, The Young Crystallographers Satellite meeting, University of Kent, Canterbury, UK
‘Structural studies of proteins involved in bacterial diseases', July 2004, Collaborative meeting and presentation at the University of Tokyo, Japan
‘Structural studies of proteins from pathogenic bacteria', Summer 2004, short presentation at Bristol Protein Crystallography Summer School, Bristol, UK
- Ordinary member of the British Crystallographic Association (BCA) from 2002-2010.
- Committee member of the Young Crystallographers Group (YCG) representing the Biological Structural Group (2007-2009); I have also chaired a session at the Young Crystallographers satellite meeting, 2009, Loughborough University and represented YCG at numerous BCA Biological Structural Group committee meetings.
- Ordinary member of the Tetrapyrrole Discussion Group (TPDG) from 2007-2010 .
Courses/workshops/training seminars attended:
- 'How to write successful grants' and ‘Opportunities in Interdisciplinary research' workshops, 2009, Educational and Staff Development, QMUL
- Fellowship Days, 2008 and 2009, Educational and Staff Development, QMUL
- BBSRC New generation conference and workshop, 2008, Newcastle ‘Introduction to Leadership and Managing Teams' workshops by Dr Fiona Stephen, September 2008,Educational and Staff Development, QMUL
- Business Plan Competition workshop, 2007, Educational and Staff Development, QMUL
- Intellectual property workshop, December 2007, QMUL
- ‘Protein characterisation seminar', 31st January 2006, Diamond House, Oxfordshire
- CCP4 study weekend, 6th-7th January 2006, ‘Crystallography of complexes', University of Leeds
- CCP4 study weekend, January 2005, ‘Data Collection and Analysis', Reading University
- Bristol Protein Crystallography Summer School, 2004, Bristol
Honors and awards
- Award for outstanding talk on 'Crystal structure determination of hemoglobin from two sturgeon species of fish, Acipenser persicus and Acipenser stellatus', 13th Conference on Biological Chemistry (CBC), 2015, Ardabil, Iran
- Certificate on ‘Biacore Basic Training', July 2011, GE Healthcare
- Certificate on ‘Introduction to Leadership and Managing Teams', July 2009, Institute of Leadership and Management (course organized by Educational and Staff development, Queen Mary University of London)
- David Blow poster prize for poster entitled ‘The Methyltransferases of cobalamin (vitamin B12) biosynthesis', British Crystallographic Association Spring meeting, April 2009, Loughborough University
- Bursary to attend the BBSRC New Generation conference, 2008, Newcastle
- Runner up in ‘pitch your idea' Business plan competition for the idea of an innovative compact gel documentation system. Received £500 Prize and certificate for my Business plan idea and pitch which was conducted in Dragon's Den style, 2007, Educational and Staff development, Queen Mary University of London. Following this success I now have an invention which I intend to have a patent filed for in the near future.
- Arnold Beevers Bursary to attend the British Crystallographic Association Spring meeting, 2005, Loughborough University
- Bursary to attend the Bristol Protein Crystallography Summer School, 2004, Bristol
- Westfield Trust prize for Outstanding Academic Achievement, 2003, Queen Mary University of London
1- Arefeh Najafi (MSc)
2- Hossein Dabbaghi (MSc)
3- Fouad Mehraban (PhD)
4- Zahra Seraj (PhD)
1- Structural and functional studies of protein in health and disease
2- Macromolecular X-ray Crystallography I
3- Macromolecular X-ray Crystallography II