Piet Borst


Piet Borst is emeritus professor of Clinical Biochemistry and Molecular Biology at the University of Amsterdam, and the former Director of Research and Chairman of the Board of Directors of the Netherlands Cancer Institute and the Antoni van Leeuwenhoekziekenhuis, where he still works as staff member.

Career

Piet Borst studied medicine in Amsterdam from 1952 to 1958 and completed his internships in 1961-1962. He received his PhD for an investigation of tumor mitochondria.
He then moved to New York City, where he worked with fellow post-doc Charles Weissmann on replication of bacteriophages in the lab of Nobel laureate Severo Ochoa. In 1965, he became professor of Biochemistry at the University of Amsterdam and head of the section for Medical Enzymology and Molecular Biology of the Amsterdam Biochemistry Department. From 1972 to 1980 Borst was also part-time Director of the Institute of Animal Physiology of the University of Amsterdam where he set up the first Unit for Molecular Biology on the Biology Campus.
In 1983 Borst moved to the Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital where he became director of research and in 1987 also chairman. He retained an honorary professorship at the University of Amsterdam. After his mandatory retirement in 1999, Borst became a staff member of the NKI-AVL and continued running his lab, studying mechanisms of chemotherapy resistance in cancer cells, the physiological functions of drug transporters and the biosynthesis and function of DNA Base J, a new base in DNA, discovered in trypanosomes in the Borst lab.
Borst has contributed in various ways to discussions about science and science policy in the Netherlands: In the seventies he was spokesman for science in the rather virulent discussions on recombinant-DNA experiments; as a director of the cancer institute he regularly reported on advances in cancer research/treatment in the press and on radio/TV; he was a member of the Innovation Platform, a small thinktank of the Dutch prime-minister; and for 23 years he wrote a monthly column in the prime intellectual dayly, the NRC-Handelsblad.

Major international organisational functions

  1. The malate-aspartate shuttle, a new major route for the transport of reducing equivalents from cytosol to mitochondria.
  2. Bacteriophage RNA replicase keeps the template and daughter strand separated during RNA synthesis; duplex RNA is not an intermediate in RNA synthesis, but an isolation artifact.
  3. Mammalian mitochondrial DNA consists of small duplex circles that are identical in sequence, as proven by quantitative DNA renaturation experiments. It follows that the bulk of mitochondrial proteins is not encoded in mitochondrial DNA, but must be imported.
  4. Development of ethidium-agarose electrophoresis ; proof that linear DNA molecules move like snakes through the gel.
  5. The glycosome, a new peroxisome-like organelle that contains the glycolytic enzyme system in trypanosomes and related uni-cellular parasites.
  6. Mitochondrial genes of the yeast Saccharomyces may contain introns .
  7. A DNA transposition mechanism for antigenic variation in African trypanosomes .
  8. Transsplicing as an essential step in the synthesis of all trypanosome mRNAs .
  9. Growth and contraction of chromosome ends, the telomeres ; trypanosome telomeres end in repeats of n later also found in human telomeres.
  10. Introduction of PFG electrophoresis for the separation of chromosome-sized DNA molecules of several protozoa .
  11. The first prenatal test for the Zellweger syndrome, a deadly inborn error of peroxisome biosynthesis.
  12. Protective physiological functions of drug-transporting P-glycoproteins, i.a. in the blood-brain barrier and in the gut .
  13. Proof that the Mdr2/MDR3 P-glycoprotein is a phosphatidylcholine translocator, essential for bile formation.
  14. Identification of the first ABC-transporter in a protozoal parasite, Leishmania, the PGP-A gene. This transporter gene is associated with arsenite resistance and is surrounded by direct and inverted DNA repeats facilitating gene amplification . This was the first representative of the ABCC class of transporters. Later Ouellette showed in his own lab that LtpgpA is an arsenite-GSH transporter involved in antimony resistance in patients.
  15. J, a new base in the DNA of trypanosomes and related parasites .
  16. Variation in the transferrin receptor allows African trypanosomes to efficiently take up transferrin in a range of mammals, notwithstanding the rapid evolution of mammalian transferrins .
  17. Biosynthesis of base J and identification of J as an essential termination signal in RNA synthesis in Leishmania.
  18. The MRP family of drug transporters has multiple members . Identification of new endogenous substrates for MRP3 and BCRP : phyto-estrogen conjugates ; MRP4 : prostaglandins ; and MRP5 : N-lactoyl-amino acids, a novel metabolites of mammals, and glutamate-conjugates.
  19. The first mouse tumor model suitable for studying mechanisms of primary and acquired resistance against drugs used to treat cancer patients .
  20. Identification of new factors inhibiting DNA end resection, REV7 and HELB, contributing to drug resistance in a mouse mammary tumor model.
  21. Identification of the Volume-Regulation Anion Channel, as a contributor to uptake of Pt-based anti-cancer drugs in cells.
  22. Pseudoxanthoma elasticum, an inborn error of calcification due to absence of MRP6 in the liver, is caused by low plasma pyrophosphate. MRP6 mediates ATP export from cells and this is rapidly converted into PPi by ectonucleotidases.