Jane GrasbyProfessor Jane A. Grasby

Professor of Biological Chemistry

Room: C83

Tel: +44-(0)114-22-29478

Fax: +44-(0)114-22-29436

email:

 

 

Biographical Sketch

Professor Grasby obtained her BSc in Chemistry from the University of Birmingham in 1988. After obtaining her PhD in Biochemistry from the University of Southampton in 1992, she became a Research Fellow at the Laboratory of Molecular Biology in Cambridge. In 1994 she was appointed to a Lectureship at the University of Sheffield, where she was promoted to Senior Lecturer in 1999, Reader in 2002 and a Personal Chair in 2013. Prof. Grasby has acted as Chair of the Faculty of Science Equality Diversity Committee.

Research Keywords

Catalysis, protein and nucleic structure and function, nucleic acid chemistry, molecular recognition, enzymology

Teaching Keywords

Organic Chemistry; Biological Chemistry

Selected Publications:

Research Interests

The interactions and reactions of nucleic acids are fundamental to life. Our research has seeks to understand these processes using a range of techniques including chemical synthesis of modified nucleic acids, molecular biology, enzymology, biophysics (fluorescence, CD and NMR spectroscopies) and X-ray crystallography. We are particularly interested in the catalysis of reactions of nucleic acids (RNA and DNA) and most recently in the question of how structure, but not sequence, specific nucleases achieve specificity in nucleic acid hydrolysis.

Human FEN1 with a single-stranded DNA flap threaded through the helical arch emerging from the hole in the proteinFlap endonucleases (FENs, shown below human FEN1 (hFEN1) with DNA substrate) have been the focus of much of our recent work. FENs are a vital component of the lagging strand DNA replication apparatus in all organisms and also play role in DNA repair in eukaryotes. FENs remove 5’-single-stranded protrusions to double-stranded DNA known as flaps, formed as a result of DNA polymerase strand displacement synthesis. In humans FENs have to carry out approximately 50 million phosphate diester hydrolyses to allow replication of a single cell. FEN1 is the prototypical member of a superfamily of structure-specific 5’-nucleases whose differing activities span all the major DNA metabolic pathways.

Each of the 5’-nucleases acts on a different substrates. Recently, we have been trying to understand both common features of 5’-nucleases and the specialised mechanisms they use to carry out their extraordinary feats of molecular recognition. We have a learnt that the single stranded DNA flap is threaded through a hole in the protein known as the helical arch. This threading mechanism allows the enzyme to act on discontinuous flap DNAs that have free 5’-ends, but importantly not at single-strand double-strand junctions in DNA that are continuous. The DNA becomes threaded through the arch while this region of the protein is disordered. Forming the helical structure delivers key amino acid residues to the active site to catalyse phosphodiester hydrolysis.

Teaching Section

Organic Chemistry

Undergraduate Courses Taught

  • "Organic Chemistry 3" (Year 1)
    This segment introduces methods for the synthesis of carboxylic acid derivatives and discusses their reactions.
  • “Chemistry Around Us 2” (Year 1)
    Four Molecules That Changed the World
  • "Introduction to Chemical Biology & Medicinal Chemistry" (Year 3)
    This course introduces the basic principles of chemical biology and medicinal chemistry
  • "Skills for Success" (Year 3; Segment Leader)
    The Skills for Success Project aims to ensure that students identify and develop skills that will be of use to them in life, future study and employment and provide a basis from which they can undertake further training of a professional nature.

Tutorial & Workshop Support

  • First Year General Tutorials.
  • Second Year Organic Chemistry Tutorials.
  • Third Year Workshops.
  • Third Year Literature Review.

Laboratory Teaching

  • First Year Lab demonstrating.
  • Second Year Lab demonstrating.
  • Fourth Year Research Project.

Journal articles

Chapters

  • Grasby JA, Young KJ, Gill F & Vyle JS (1996) The hairpin ribozyme In Meunier B (Ed.) (pp. 295-306).

Conference proceedings papers

  • Finger LD, Bennet IA, Hounslow A, Exell JC, Baxter NJ, Waltho JP & Grasby JA (2015) The Catalytic Cycle of hFEN1 Requires Protein and DNA Conformational Changes, but Are They Rate-Limiting?. PROTEIN SCIENCE, Vol. 24 (pp 147-147)
  • Osborne SD & Grasby JA (2005) Investigations into substrate analogues for Fen-1. Chemistry of Nucleic Acid Components, Vol. 7 (pp 347-350)
  • Kovacheva YS, Tzokov SB, Murray IA & Grasby JA (2002) Kinetic studies of the Neurospora vs ribozyme. CHEMISTRY OF NUCLEIC ACID COMPONENTS, Vol. 5 (pp 352-355)
  • Marsh AJ, Price C & Grasby JA (2002) Synthesis of polyamine-uridine conjugates by derivatisation at the 5-position. CHEMISTRY OF NUCLEIC ACID COMPONENTS, Vol. 5 (pp 241-244)
  • Tzokov SB, Macdonald IK, Murray IA & Grasby JA (2002) Investigating catalytic RNA molecules. CHEMISTRY OF NUCLEIC ACID COMPONENTS, Vol. 5 (pp 231-240)
  • McDonald IK, Holmes SC, Young KJ, Vyle JS, Pickering TJ & Grasby JA (1999) Functional group mutagenesis of the hairpin ribozyme. CHEMISTRY OF NUCLEIC ACID COMPONENTS, Vol. 2 (pp 306-309)
  • Pickering TJ, Garforth SJ, Sayers JR & Grasby JA (1999) Mechanistic studies of a 5 ' nuclease from T5 bacteriophage. CHEMISTRY OF NUCLEIC ACID COMPONENTS, Vol. 2 (pp 161-167)

Website content

  • Grasby JA Home Page.