Hartley was educated at
Queens' College, Cambridge graduating with a Bachelor of Arts in 1947 followed by a Master of Arts degree in 1952.[6] He moved to the
University of Leeds where he was awarded a PhD in 1952[8] for research supervised by
Malcolm Dixon and Bernard A. Kilby.[3][2]
Career and research
From 1952 to 1964, Hartley pioneered work on the sequence and mechanism of the enzyme
chymotrypsin in Cambridge, and developed the use of paper chromatography to separate amino acids and peptides — an essential part of protein characterisation at that time.[9][10] In 1965, he became a founding member of the
Medical Research Council (MRC)
Laboratory of Molecular Biology (LMB), and collaborated with
David Mervyn Blow[11] in determining the structure and mechanism of chymotrypsin, as part of extensive work on chymotrypsin and related enzymes.[12][13][14][15][16] His group also showed that mammalian
serine proteases, including the
blood clotting cascade, had
homologous structures and mechanisms, indicating a common evolutionary origin.[17] Hartley also studied other enzymes, such as aminoacyl tRNA synthetases (with
Alan Fersht),[18][19] xylose isomerase[20] and glucose isomerase.[21]
In 1974, Hartley became Head of the Department of Biochemistry at Imperial College London, converting it into a centre for
molecular biology. In 1982, he conceived the need for a discipline –
biotechnology – to exploit molecular biology breakthroughs. He left the Department of Biochemistry to set up Imperial's Centre for Biotechnology, and became a founding board member of
Biogen – the longest surviving
genetic engineering company. Since then, Hartley has founded companies to make cheap
bioethanol from waste
hemicellulosicbiomass, using genetically engineered
compost heap microorganisms.[1]
Distinguished for his studies on the structure and mode of action of the proteolytic enzymes. In particular, he has determined the complete amino acid sequence of
chymotrypsinogen, a protein of 253 residues, and has studied the relationship of this structure to enzymic activity. He has developed two important new techniques in protein chemistry: the "
dansyl" methods for determining sequences in peptides on a very small scale, and the "diagonal" technique for studying the distribution of
disulphide bridges in proteins. His comparative studies on other
pancreaticproteolytic enzymes have revealed interesting homologies, which give information about the biological origin of the proteins and their mode of action.[1]
His earlier kinetic studies on chymotrypsin demonstrated the formation of an
acyl enzyme as an intermediate in the
hydrolysis reaction.[22]
^Hartley, B.S.; Naughton, M.A.; Sanger, F. (1959). "The amino acid sequence around the reactive serine of elastase". Biochimica et Biophysica Acta. 34: 243–244.
doi:
10.1016/0006-3002(59)90254-9.
PMID14400120.
^Fersht, Alan R.; Ashford, Jeremy S.; Bruton, Christopher J.; Jakes, Ross; Koch, Gordon L. E.; Hartley, Brian S. (1975). "Active site titration and aminoacyl adenylate binding stoichiometry of aminoacyl-tRNA synthetases". Biochemistry. 14 (1): 1–4.
doi:
10.1021/bi00672a001.
PMID1109585.
^Hartley, Brian S.; Hanlon, Neil; Jackson, Robin J.; Rangarajan, Minnie (2000). "Glucose isomerase: Insights into protein engineering for increased thermostability". Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology. 1543 (2): 294–335.
doi:
10.1016/S0167-4838(00)00246-6.
PMID11150612.