Margaret A.L. Blackie
Office: 1038 De Beers Building
Phone: +27 (0)21 808-3353
Fax: +27 (0)21 808-3360
PhD, University of Cape Town (SA), 2002
Post-doc, Universite des sciences et technologies (France), 2002/3
Post-doc, University of Cape Town (SA), 2007/8
Post-doc, University of Cape Town (SA), 2009
Medicinal chemistry; chemical education; philosophy
I run a multidisciplinary research group with interests in medicinal chemistry, chemical education and the philosophy of science, education and chemistry. The focus of medicinal chemistry is the rational design and synthesis of novel compounds as potential anti-malarial drugs and other tropical diseases. My interests in chemical education and philosophy of chemistry and education are complementary to one another. The primary endeavour is to develop curricula, tools and educational aids with a solid foundational philosophy in order to better prepare the next generation of chemists.
Research Descri ption:
Malaria continues to be a major health problem. Over 3.2 billion people are infected each year resulting in at least one million fatalities. The vast majority of these deaths occur in sub-Saharan Africa and of these, over 90% are children under the age of 5. In the 1950’s a campaign was launched to eradicate malaria. DDT and chloroquine were key weapons in this battle, and malaria was driven back to a point where less than 10% of the world’s population was at risk. Unfortunately drug resistance and insecticide resistance began to emerge. By the launch of the Roll Back Malaria campaign in 1998, a joint effort of the World Bank, the World Health Organization, UNICEF and the United Nations Development Program (UNDP), more than 40% of the world’s population lived in endemic areas. In the last 10 years there has been a 10 fold increase in funding for malaria research covering all aspects from drug discovery to the use of insecticide laden mosquito nets. The economic burden of malaria is substantial. In countries with endemic malaria, the annual economic growth rates over a 25-year period were 1.5% lower than in other countries. This implies that the cumulative effect of the lower annual economic output in a malaria-endemic country was a 50% reduction in the per capita GDP compared to a non-malarious country. My research aims to contribute to this battle through the use of modern synthetic organic chemistry in conjunction with suitable biological assays. In the last decade, an exciting new potential target for antimalarial drug design has emerged. The apicoplast is a small, plastid derived, organelle present in the cells of the genus Plasmodium. The apicoplast is an endosymbiont which has become a crucial organelle in the Plasmodium family.5 The apicoplast contributes roughly 10% of the genome of the Plasmodium cell. A focus on the development of antimalarial compounds which target the apicoplast specifically is a relatively new and exciting area of research. It has been established that the apicoplast is responsible for two key, parasite specific and essential, cellular processes in Plasmodium (bacterial-type isoprenoid biosynthesis and fatty acid synthesus type II, FAS II). This is significant because it provides a target for the rational design of parasite specific drug compounds. Furthermore, it provides a complementary approach to much of the medicinal chemistry research already established in this area. The principle focus of this medicinal research group is the design, synthesis and evaluation of new antimalarial compounds using established methodologies of synthetic organic chemistry. The aim would be to target essential biological pathways directly associated with the apicoplast. The design of these molecules would be based on the modification of antibiotic compounds known to have antiplasmodial efficacy such as azithromycin, doxycyclin, tetracycline etc. As an initial exploration, determination of potential key pharmacophores in these molecules would be identified and used as scaffolds for the design of simple analogues of these molecules. Some information is already available in this regard. Using an iterative process, the focus on pharmacophores directly associated with antiplasmodial activity would be established and further analogues of the biologically privileged scaffolds synthesised and tested.
Education and Philosophy
One of the perpetual questions of philosophy is – how do we know what we know? It is several levels above the fundamental questions of who am I? And why am I here?, but it is a significant question nonetheless. It is a particularly pertinent question to education. The way in which we approach the question – how do we know what we know? – influences the way in which we will teach what we think we know to the next generation. My current research is focused on looking at the answers given by three twentieth century philosophers – John Dewey: an American pragmatist. Dewey was an educationist as well as philosopher, and established an experimental school in Chicago in the late 1890’s. His primary thesis was that experience was crucial to education. We learn because we experience things. The child learns that the fire is hot because he burns himself. Dewey developed a style of education which was based on the experience of the learner. Karl Popper: a philosopher of science who wrote extensively on issues in society as well. In scientific circles Popper is best remembered for his principle of falsification. But the broader notion of critique which Popper advocates as the only way to advance knowledge is vital for any educational endeavour. Bernard Lonergan: who undertook the mammoth task of reinterpreting Thomas Aquinas in the light of the philosophy of Immanuel Kant. Lonergan strongly advocates the significance of experience. In Lonergonian terms, we learn in a sequential manner. From experience, through understanding of experience, to judgement of understanding leading finally to a decision. The capacity to make a decision is what defines knowledge. However, according to Lonergan, when we teach, we reverse the process. We give the conclusion drawn (i.e. the decision made), followed by the judgement, which was drawn from a specific understanding given a particular experience. These three philosophy bring different perspectives and emphases to education and educative process. Exploring their understanding of knowledge, experience and engagement can inform choices we make in defining how we will teach and what we will teach in order to transform students into scientists.
- Blackie, MAL; Case, JM; Jawitz, J. "Student centredness: the link between transforming students and transforming ourselves, Teaching in Higher Education", in press
- Blackie, MAL; Yardley, V; Chibale, K. "Synthesis and evaluation of phenylequine for antimalarial activity in vitro and in vivo", Bioorg Med Chem Lett, 2010, 20, 1078-1080
- Blackie, MAL; Chibale, K. "Metallocene Antimalarials: The Continuing Quest", Metal Based Drugs, 2008, Article ID 495123
- Blackie, MAL; Saravanamuthu, A; Fairlamb, AH; Chibale, K. "Inhibition of Trypanothione Reductase and Glutathione Reductase by Ferrocenic 4-Aminoquinoline Ureas", Arkivoc, 2008, 6, 52-60
- Blackie, MAL; Beagley, P; Croft, SL; Kendrick, H; Moss, JR; Chibale, K. "Metallocene-based Antimalarials: An exploration into the influence of the ferrocenyl moiety on in vitro antimalarial activity in chloroquine sensitive and chloroquine resistant strains of Plasmodium falciparum", Bioorg. Med. Chem., 2007, 15, 6510
- Blackie, MAL; Beagley, P; Chibale, K; Clarkson, C; Hutton, AT; Moss, JR; Smith, PJ. "Synthesis and antimalarial activity in vitro of new heterobimetallic complexes: Rh and Au derivatives of chloroquine and a series of ferrocenyl-4-amino-7-chloroquinolines", J. Organomet. Chem., 2003, 1016
- Chibale, K; Moss, JR; Blackie, MAL; van Schalkwyk, D; Smith, PJ. "New amine and urea analogues of ferrochloroquine: synthesis, antimalarial activity in vitro and electrochemical studies", Tetrahedron Lett., 2000, 41, 6231