1. Current Projects Blood Substitutes Mechanisms of Acute Kidney Injury Metal Isotope and Magnetic Field Effects on Protein Kinases Structure and Function of Non-Symbiotic Plant Haemoglobins Biophysics and Physiological Function of Human Cytoglobin

2. Pentacoordinate Globins: A: Sperm Whale Myoglobin B: Human Haemoglobin  chain C: Yellow Lupin Leghemoglobin Hexacoordinate Globins D: Human Neuroglobin E: Human Cytoglobin F: Asian Rice Non-Symbiotic Haemoglobin Haemoglobin Superfamily: Reeder, B.J. Antioxid. Redox. Sign. (2010) 13(7) 1088-1123

3. Interaction of Cytoglobin with lipids changes structure of the protein Various Lipids and Lipid-like molecules cause a change from 6 to 5 coordinate iron ligation state Reeder, B.J., Svistunenko, D.A. & Wilson M.T. “Lipid binding to cytoglobin leads to a change in haem co-ordination: a role for cytoglobin in lipid signalling of oxidative stress” Biochem. J. (2011) 434, 483–492 Stopped FlowLaser Flash EPR

4. What is the Mechanism of the Cytoglobin Cell Protection?

5. Haemoglobins in Plants Non-symbiotic plant haemoglobins (nsHbs) Discovered from genomic sequencing in mid-90s. Three classes of nsHbs: Class 1 nsHb: related to leghaemoglobin, but with hexacoordinate haem iron. Expressed in both roots and rosette leaves. Forms stable O 2 complex with very high O 2 affinity (K d ~2-10nM). Known structure for rice and corn (but not Arabidopsis-until now). Class 2 nsHb: Hexacoordinate globin ~60% sequence homology to class 1 proteins. Lower O 2 affinity (K d ~150nM). Induced in rosette leaves at low temperatures. Very high auto-oxidation rate. No structures known. Class 3 nsHb: Sequence suggests a truncated 2/2 α- helical structure like bacterial truncated Hb. Very little information available. Very few papers. No structures known.

6. Crystal Structure of A. thaliana Hb3 Comparison of AHb3 structure (red) with haemoglobin from Bacillus subtilis (blue) AHb3 Structure to 1.77 Å Resolution

7. Magnesium Isotope and Magnetic Field Effects on Creatine Kinase Activity

8. Earthquakes and Acute Kidney Injury The Spitak Earthquake (Armenia 1988) 25,000+ casualties Rhabdomyolysis Acute Kidney Injury 600-1000 survivors developed Rhabdomyolysis of which 225-385 developed Acute Kidney Injury (Acute Renal Failure). Many fatalities due to inadequate renal treatment facilities (dialysis machines) In England up to 750,000 are effected by Acute Kidney Injury at a cost of ~£600 million to NHS (5-25% due to rhabdomyolysis).

10. Reeder, B.J., Grey, M., Silaghi-Dumitrescu, R., Svistunenko, D.A., Bülow, L., Cooper, C.E. & Wilson, M.T “Tyrosine residues as redox cofactors in human hemoglobin: Implications for engineering non toxic blood substitutes” J. Biol. Chem (2008) 283(45), 30780-30787 Blood Substitutes Can we Engineer a less toxic blood substitute?

11. Current/Developing Collaborations: Cytoglobin: Dr Dima Svistunenko (Essex) Prof Geoff Moore (UEA) Dr Marten Vos (Ecole, France) Dr Philippe Laissue (Essex) Dr Metodi Metodiev (Essex) Plant Haemoglobin:Dr Mike Hough (Essex) Prof Leif Bulow (Lund, Sweden) Prof Phil Mullineaux (Essex) Dr Dima Svistunenko (Essex) EMF:Prof Mike Wilson (Essex) Dr Gary Silkstone (Essex) Prof Robert Hider (Kings C., London) Acute Kidney injury: Professor Kevin Moore, UCL Prof Chris Cooper (Essex) Prof L. Jackson Roberts II (Vanderbilt, USA) Dr Sinan Battah (Essex/UCL) Blood Substitutes: Prof Chris Cooper (Essex) Dr Gary Silkstone (Essex) Prof Andrea Mozzarelli (Parma, Italy) Prof Leif Bulow (Lund, Sweden)