Dr Alison Parkin

01904 322561
Email: alison.parkin@york.ac.uk

Contact Alison for opportunities in the group

Research

Electrochemical insights into redox-active metalloproteins, bacterial metabolism and catalysis

Research

I am interested in how oxidation state changes at transition metal centres in proteins activate chemical reactions which are essential for life. Understanding such processes is important across a wide range of fields: a fundamental understanding of how bacteria derive the energy for life is essential if we are to develop new antibiotics to halt the rise in drug-resistant pathogens; learning how H2 and other small molecule activation occurs efficiently and rapidly at non-precious metal centres teaches us how to design better industrial catalysts; and finding out how novel proteins function in humans reveals how we work as big reaction vessels of living chemistry.

In the laboratory the main technique used to interrogate these redox reactions is film electrochemistry. This method permits precise control of the reduction-potential of the protein so that measurement of current provides a quantitative measure of the rate of redox reactions. Thermodynamic and kinetic reaction parameters are determined quantitatively, and enzymatic reaction mechanisms can be probed through analysis of substrate catalysis and inhibitor sensitivity. To complement the functional insight that electrochemistry provides, structural information is determined with molecular biology, protein crystallography, electron paramagnetic resonance and infra-red spectroscopy.

H2 as a fuel in bacterial disease

Hydrogen oxidation derives ATP synthesis

Structure of hydrogenase-1 from E. coli

In living cells, oxidation and reduction reactions are coupled together across a membrane to generate electron gradients which ultimately provide the energy for ATP synthesis and life. Many disease causing bacteria are able to use H2 as a fuel in this process, with H2 uptake (H2  2H+ + 2e-) having proved very important in enabling SalmonellaMycobacterium tuberculosis and Helicobacter pylori (a stomach cancer-causing agent) to survive. The function and structure of these enzymes and the biosynthetic pathways of assembly will be probed to understand how this chemistry works and how it can be shutdown in order to try and develop new antibiotic drugs. Research in this area is in collaboration with Professor Frank Sargent (University of Dundee) and Professor Greg Cook (University of Otago, New Zealand).

Technologically useful bio-catalysts

Technologically useful bio-catalysts

Microbes are fantastically inspirational chemical factories: they produce highly efficient and active catalysts which use common metals and often operate at standard temperature and pressure. Much of the small molecule chemistry which occurs in bacteria is industrially important to humans and studying the enzymes which catalyse this chemistry can teach us how the transition metal centres function. We can then manipulate the DNA of the bacteria in order to force the bacteria to biologically synthesis novel ligand environments to specifically re-tune the chemical specificity. Some of the enzymes being studied are:

  • Acetylene hydratase catalyses the reaction HC≡CH + H2O → HC(O)-CH3. This is an important example of C-H bond activation, a class of reactions of fundamental importance to organic synthesis. This project is in collaboration with Dr John Slattery (York) and Professor Neil Bruce (York).
  • Polysaccharide oxygenases are Cu-dependent enzymes important in the breakdown of chitin, cellulose and other recalcitrant polysaccharides which may play a critical step in the development of biofuel technologies. This project is in collaboration with Professor Paul Walton (York) and Professor Gideon Davies (York).
  • Nitrate reductase catalyses NO3- + H2O + 2e- → NO2- and has applications in the development of galvanometric biosensors for water quality measurement. This project is in collaboration with Professor Paul Walton (York) and Professor Joel Weiner (University of Alberta, Canada).

Method development

Targets for method development

Film-electrochemical measurements of proteins are sometimes hampered by limited surface-adsorption and large background signals. To overcome these problems recent developments in alternating-current instrumentation and methodology are being explored to enhance the signal and deconvolute electron-transfer and chemical rates. Novel surface chemistry approaches are also being explored.

Group Members

Parkin Group Members

 

Alison Parkin

null

Alison Parkin arrived in York in October 2012 and is currently enjoying setting up her research group which focuses on exploring the mechanism of biological redox catalysis using electrochemistry. Alison is interested in how microbial enzymes can inspire the development of novel biotechnology, and the structure-function relationship which controls such chemistry. Her group develops new techniques as well as exploring new systems, including H2-redox enzymes, Mo-enzymes of unknown function, and Cu-cellulase proteins. Alison is doing some teaching for Pauling College Chemistry students and the 2nd year Biochemists. Alison originally hails from Yorkshire and has returned to 'God's own county' after a 12-year spell in Oxford where she did her MChem and DPhil at Jesus College and a Junior Research Fellowship at Merton College. Outside the lab she doesn't enjoy cycling but does it anyway to try and stay fit! 

Julia Walton

null

I'm the technician for the Parkin-Fascione Groups two days a week, and provide technical support in the NMR centre for two days a week also. I studied Joint Honours Chemistry and Biochemistry at Nottingham University, and then worked in the Biotechnology Industry as a Biochemist for several years. I was lucky enough to be a Process Development Scientist for Bayer AG in San Francisco for two years where I helped to develop processes for the production and characterisation of the recombinant protein Factor VIII, which is used in the treatment of haemophilia. After moving back to the UK I joined YSBL here in York, where I worked on many projects including characterising the structure of the Oestrogen receptor protein. After a brief spell as a technician in teaching labs, I moved to my current role 3 years ago. Outside of work I enjoy photography, reading and looking after my three cats!  

 Ben Aucott

Ben Aucott

I am a PhD student shared with Jason Lynam and Ian Fairlamb. My research involves synthesizing transition metal carbonyls and probing their redox properties for therapeutic applications. I enjoy the wide-ranging, interdisciplinary nature of this work. I came to York in 2014 after an MChem at Wadham College, Oxford, where I studied hydrogenase inhibition using spectroelectrochemistry in the group of Professor Kylie Vincent. You might also find me learning about natural history, supporting the mighty Nuneaton Town FC, or attempting various complex aerobics routines.

Sophie Berrell

null 

I am a first year PhD student shared with Alison Parkin, Peter O’Brien and Victor Chechik. My research involves the late-stage functionalisation of drug-like scaffolds by electrochemically-generated free radicals. I graduated from the University of Leeds (MChem with an industrial placement year). The placement involved research of an opioid addiction treatment drug and its impurities in order for the drug to be approved.

Mark Dowsett

null

I am a first Year PhD student working on electrochemical CO2 capture and mineralisation. The project currently has a working cell with a platinum cathode and a mixed graphite/aluminium anode that uptakes CO2 as well as producing hydrogen. I hope to utilise this hydrogen to upgrade CO2 to fuels such as methanol of higher alcohols or hydrocarbons. In my own time I like to play badminton and archery.

Nick Yates

null

I work on the site selective bio-orthogonal modification of proteins with the aim to covalently crosslink proteins to electrode surfaces in orientations suitable for facile electron transfer, and the subsequent electrochemical assay of these immobilised protein. My work will allow for the electrochemical assay of redox proteins that have proved difficult to analyse by classic protein film voltammetry, allowing the mechanism of these proteins to be probed and kinetic information to be obtained. Immobilisation of proteins via a covalent bond also increases the lifespan of the immobilised protein film, improving the performance of redox proteins as electrocatalysts.

Christopher Orme

null

I’m a first year PhD student researching the late-stage functionalisation of agrochemical-type scaffolds by electrochemically-generated free radicals. I graduated from the University of York (MChem: Chemistry, Biolgical and Medicinal Chemistry with a year abroad) undertaking my MChem project at Victoria University of Wellington. Research focused on the synthetic approaches towards the total synthesis of (-)-TAN-2483B; a secondary fungal metabolite which is a lead as a novel kinase inhibitor. 

Nicola Williams 

 Nicola Williams

I completed a BSc in Biochemistry at the University of York (I completed my research project working with the Parkin research group) and I am continuing to study here for an MSc by research. I am enjoying my MSc project very much- I am using protein film electrochemistry to further characterise the catalytic mechanism of bacterial molybdenum enzymes. I also enjoy going to Chemistry Department seminars, learning Japanese (I would love to go to Japan one day) and playing piano and oboe.   

Huw Watts

null

I enjoyed my undergraduate at York, and decided to study my masters here too. My research project studies a bacterial molybdo-enzyme, and hopes to compare its activity with homologous proteins. Chemically, my interests include bioninorganic and organometallic systems. Outside the lab, I play the violin and dancing (but only when no one can see me). 

 Catherine Lowe

null

I am a fifth year biochemistry integrated masters student currently studying the enzyme laccase and its applications in synthetic chemistry. I will be using electrochemistry to characterise the activity of laccase and any mutants that will be generated. Outside of the lab I like to keep fit, watch/play rugby league and researching ways to feed my wanderlust.

Owen Jarman

null

I am a final year MChem student using electrochemistry, specifically protein film Fourier transform voltammetry, to study various redox proteins such as DsbA. To achieve this I am engineering aldehyde groups on proteins and crosslinking these to modified electrode surfaces. Outside of labs I enjoy blasting out tunes on the trumpet in brass band and going cycling and running.

 

 

 

 

 

 

Gallery

Parkin Group Photos

Parkin Group 2016

 

Meal with summer students

meal with summer students

 

Summer BBQ 2015

bbq

 

Alison and Hope visit collaborators in Australia

Reading papers at the beach  Meeting Ian Dance at the Sydney Opera house

Seminar in Melbourne

Alison with Alan at the footy group meal ‌Hope with a Koala

 

Christmas Party 2014 - Pizza and liquid nitrogen icecream

xmas party icecream

 

Welcoming new lab members

lab curry

 

Summer student Aaron falls in love with Betty the glovebox

Betty the glovebox   Aaron and Betty

 

Lab move summer 2014

Hope lab move   Julia lab move

 

End of year BBQ 2014

 

End of term meal at Il Paradiso

Photo of group at il paradiso

photo at il paradiso

 

David enjoying his birthday with a caterpillar cake

Photo of David   Photo of David's birthday

 

Hope at work in the glovebox 

Photo of glovebox   ‌

 

Parkin group - hard at work

Photo of Harriet and Lindsey   Photo of parkin group

 

‌  ‌

Alumni

Gone but not forgotten

Parkin Group Leavers 2014

Photo of Alison Parkin's group. 

Harriet Chidwick  MChem student

Worked on hydrogenase oxygen tolerance and supplying the Parkin lab with laughter and biscuits. Now a PhD student in the Fascione group (York).

Charlotte Neil  MChem student

Studied CO releasing molecules and introduced Disney music to the Parkin lab. Now a trainee accountant at Sam Rogoff & CO (London).

Emily Brooke  MChem student

Worked on copper lytic polysaccharide monooxygenases and bringing a touch of class to the Parkin group. Now a PhD student in the Armstrong group (Oxford).

Alison Fellgett  Biochemistry project student

Worked on whole cell electrolysis for hydrogen production and how not to turn cells pink. Now a research technician (York).

David Lloyd  Biochemistry project student‌

Developed a hydrogenase activity assay and left with the glory of being crowned BMTron champion. Now a research scientist at Sense Biodetection (Oxford).

David Lloyd champion

Parkin Group Leavers 2015

Group photo

Jonathan Balbach  MChem student

Worked on understanding the biosynthetic pathway of Salmonella enterica hydrogenase-5 and naming every piece of equipment in the Parkin / Fascione labs.

Sam Lobato

Studied copper lytic polysaccharide monooxygenases.

Alec Banner  Biochemistry project student‌

Worked on acetylene hydratase enzymes and adding a bit of muscle to the Parkin lab. 

Chileab Redwood-Sawyerr  Biochemistry project student‌

Studied molecular biology of hydrogenases.

Jess Munro  Biochemistry project student‌

Worked on whole cell electrochemistry of Methanococcus maripaludis for hydrogen production.

Jonny boy