Bulletin Spring‧Summer 1994

Researcher getting two automatic DNA sequencers into action simultaneously Picking recombinant cDNA clones in a sterile hood mRNA species expressed in the heart. B y extracting the DNA material from the clones and amplifying its amount via polymerase chain reaction, the DNA can be purified and sequenced directly. To 'sequence' a DNA means to delineate the biochemical structure and pattern of its constituent genes. The sequences obtained were then compared with published sequences i n an international database. Of the 1,000 cDNA clones randomly chosen for sequencing, 24 per cent matched with published human sequences, 10 per cen t matched with mitochondria sequences (mitochondria are subcellular organelles that function as the machinery for cellular respiration), and 6 per cent matched with repetitive human sequences. Bu t the rest, nearly 60 per cent, turned out to be novel — these are genes associated with the heart that have never been seen before. Two Genes Studied in Depth Unfortunately, studying 600 genes would be too much of an undertaking for the research team. So they focused their effort on two novel cDNA genes of particular interest. The first, A076, contains a region the structure of which corresponds to heat shock proteins. It has been demonstrated that changes in the level and distribution of such proteins have a direct bearing on the evolution of atherosclerosis, i.e. the progression from fatty streaks to fibrous plaques that can block an artery, producing a heart attack. It is also thought that heat shock proteins are produced during stress and may protect cells by preventing damage of other important cellular proteins, or by restoring the functions and properties of damaged proteins. The other gene of interest, A0550, contains a cDNA which shares the same structural origin with zinc-binding proteins. Zinc-binding proteins ma y have a variety of functions including zinc transport and specific interactions with DNA, RNA or proteins. Application Researchers hope that they can use these novel genes as probes to find suitable markers that correlate the genetic changes with human genetic diseases, thereby facilitating diagnosis of genetic heart diseases and the identification of individuals who might be prone to certain health conditions. The mysteries of the heart are being unfolded gene by gene. Investigators DR.Mary Waye read bacteriology and immunology at the University of Western Ontario and earned her B.Sc. (Hon.) in 1976. Shefurthered her studies at the University of T o r o n t o , specializing in medical biophysics, and was awarded the degree of Ph.D. in 1982. Dr. Waye was assistant professor at the Department of Dentistry in the University of Toronto before joining this university as lecturer in biochemistry in 1992. Prof. Lee Cheuk Yu studied biochemistry at the University of British Columbia in Canada, where he received his Ph.D. He was postdoctoralfellow and later assistant professor at the New England Institute, USA, before joining the Department of Biochemistry of The Chinese University as lecturer in 1972. He was promoted to professorship in January 1985. Research Projects 20