Prof L Birkholtz

Office:  7-7 Agriculture Building

Tel: 12-420-2479

Fax: 12-362-5302

E-maillynmarie.birkholtz [at] up.ac.za

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Malaria Parasite Molecular Laboratory (M2PL)


Background

Prof Lyn-Marie Birkholtz obtained a BSc in Genetics, Human Physiology and Biochemistry, and a BSc (Hons) and MSc in Biochemistry cum laude at the University of Pretoria. Her PhD study on biochemical aspects of malaria was completed in 2003, eight months of which was spent in laboratories in the USA and Germany, which subsequently led to a collaborative post-doctoral study with Germany. She is currently an associate professor in the Department of Biochemistry at the University of Pretoria.

Current research interests

Prof Birkholtz has been investigating unique properties of the malaria parasite in order to discover parasite proteins that can be targeted with novel antimalarial drugs. In an innovative approach, she combines cutting-edge technologies (such as structural and functional genomics strategies) to identify caveats in the malaria parasite biology that can be targeted and would result in parasite death. A particular focus is on polyamine metabolism, as the parasites are essentially and totally dependent on these polycations for normal division and differentiation. The biochemical elucidation of the polyamine pathway and structural characterisation of key proteins indicated unique parasite-specific characteristics of a novel enzyme complex that could be exploited in the design of alternative, parasite-specific chemotherapies. New knowledge on certain less well understood biological phenomena characteristic of the malaria parasite (e.g. gene regulatory mechanisms and cell cycle control) is being revealed using structural and functional genomic approaches. The application of functional genomics strategies in drug target and therapeutics discovery is employed in validation and mode-of-action determination of novel potential antimalarials from indigenous herbal medicines and herbicides.

 

Current activities and collaborations

  • Member of the University of Pretoria Centre for Sustainable Malaria Control (UPCSMC) with projects focussed on alternative biological systems for malaria control.

  • Member of the European Virtual Institute for Malaria Research (EviMalar, EU Pf7 funded) with a research focus on ‘Cell cycle control in malaria parasites through epigenetic mechanisms’. Collaboration with Prof M Llinas (Princeton University) and Prof C Doerig (Monash University).

  • Polyamine analogues as novel antimalarials influencing cell cycle control in malaria parasites. Collaboration with Prof P Woster (Medical University of South Carolina) and Prof R Casero (Johns Hopkins).

  • Functional genomics investigations of malaria parasites under drug pressure. Collaboration with Prof M Llinas (Princeton University, USA) and Dr E Marechal (CNRS, France).

  • Structure-function analysis of key enzymes in the polyamine metabolic pathway of the malaria parasite. Collaboration with Dr C Wrenger and Prof RD Walter (Bernhard Nocht Institute for Tropical Medicine, Germany), Prof O Heby (Omea, Sweden) and Prof L Persson (Lund University, Sweden)

  • Investigations of polyamine transport mechanisms. Collaboration with Prof K Kirk (Australian National University, Australia), Prof Otto Phanstiel (University of South Florida) and Animex Corp, USA.


Other relevant information

Prof Birkholtz has received numerous international scientific awards, including a Mellon Foundation Mentorship Grant for her PhD studies; Trends in Parasitology best poster presentation award at the Molecular Aspects of Malaria Meeting, Lorne, Australia; IUBMB and ACGT fellowships and Exceptional Young Scientist Award, University of Pretoria 2010. She is a grant holder of EU PF7, NRF, NRF Thuthuka, MRC, SAMI as well as bilateral scientific exchange grants with Germany, Sweden, Australia and the UK.

She is the author of numerous scientific publications amongst which invited review publications. Prof Birkholtz has been an invited speaker at several national and international conferences and presented her research at invited international seminars. She serves on the scientific advisory panel for the International Polyamines conference, and is a member of the editorial advisory panel of the Biochemical Journal.

Currently (2011), 5 PhDs, 11 MSc’s and 14 BSc (Hons) students have completed their studies under her co-supervision and supervision (9 females, 3 males, 5 designated groups). She is currently supervisor of 4 BSc(Hons), 5 MSc and 5 PhD students and co-supervisor of 1 MSc and 1 PhD student. Most students in the malaria research program have NRF (prestigious/scarce skills) bursaries and also received several fellowships and awards during the course of their studies including travel grants (e.g. ACGT travel grants x2; Bill and Melinda Gates Foundation Travel grant x2; NRF International Travel Block Grant: x2; Wellcome Trust Travel Fellowships x4; ICOPA travel grants x4); research visit grants (DAAD x2; IUBMB x3; UP Study Abroad bursaries x4; AusAID fellowship x1; NRF mobility grants x2); prestigious fellowships and scholarships (TATA Africa x1; Carl and Emily Fuchs x2; Claude Leon Postdocs x2; Mellon Foundation PhD fellowships x3; Ernst and Ethel Ericksen Trust x2) and other awards (Best BSc Hons student x6; Best MSc student x5; S2A3 Bronze Medal for best MSc thesis x1; Merck Gold Medals for best final year Biochemistry students x6; Roche Biochemicals prize for best Hons student at national level x1).

Prof Birkholtz is member of the International Biochemical Society, the South African Malaria Initiative (www.sami.org.za), the University of Pretoria Centre for Sustainable Malaria Control, the European Virtual Institute for Malaria Research (www.evimalar.org), the South African Society of Biochemistry and Molecular Biology and the African Centre for Gene Technologies (www.acgt.co.za)

In addition, Prof Birkholtz teaches undergraduate courses in Biochemistry and is furthermore coordinator of the BSc (Hons) and BSc (Hons Biotechnology, Biochemistry) courses. Prof Birkholtz leads the Postgraduate studies subcommittee of the Department of Biochemistry. She has acted as reviewer to NRF grants as well as to peer-reviewed scientific publications.

 

 

Recent publications

1.      Verlinden B, Niemand J, Sharma SK, Banley RJ, Woster PM and L Birkholtz. Discovery of novel (bis)urea and (bis)thiourea-alkylated polyamine analogues with potent antimalarial activities. J Med Chem (in press). Impact factor 5.2

2.     Williams M, Sprenger J, Human E, Al-Karadaghi S, Persson O, Louw AI and L Birkholtz. Biochemical characterisation and novel classification of monofuncitonal S-adenosylmethionine decarboxylase of Plasmodium falciparum. Mol Biochem Parasitol (In press). Impact factor 3

3.     Birkholtz L, Williams M, Niemand J, Louw AI, Persson L and Heby O. Polyamine homeostasis as a drug target in pathogenic protozoa: peculiarities and possibilities. (2011) Invited review. Accepted: Biochem J (In press). Impact factor 5.1

4.     Becker J, Mtwisha L, Crampton B, Stoychev S, AC van Brummelen, S Reeksting, AI Louw, L Birkholtz and D Mancama (2010). Spermidine synthase inhibition of Plasmodium falciparum indicates perturbation-specific effects in the transcriptome and proteome. BMC Genomics. 11:1-16 Impact factor 3.93,

5.     S Smit, S Stoychev, AI Louw and L Birkholtz (2010) Extensive proteomic profiling of Plasmodium falciparum through improved semi-quantitative, two-dimensional gel electrophoresis. J Proteome Res. 9(5):2170-81. Impact factor 5.684.

6.     K Clark, J Niemand, S Reeksting, S Smit, AC van Brummelen, M Williams, AI Louw and L Birkholtz (2010) Functional consequences of perturbing polyamine metabolism in the malaria parasite, Plasmodium falciparum. Amino Acids: Special Issue: Polyamines. 38(2):633-44. Invited Review, Epub 2009 Dec 9. Impact factor 4.123

7.     de Beer TAP, Wells GA, Burger PB, Joubert F, Marechal E, Birkholtz L and AI Louw (2009) Antimalarial drug discovery: in silico structural biology and rational drug design. Infectious Disorders-Drug Targets special in silico issue. 9(3):304-18. Invited Review. Impact factor 4.9.

8.     van Brummelen AC, Olszewski KL, Wilinski D, Llinas M, Louw AI and Birkholtz L (2009). Co-inhibition of Plasmodium falciparum s-adenosylmethionine decarboxylase/ornithine decarboxylase reveals perturbation-specific compensatory mechanisms by transcriptome, proteome and metabolome analyses. JBC. Feb 13;284(7):4635-46. Epub 2008 Dec 10. Impact factor 5.8

9.     L Birkholtz, G Blatch, TL Coetzer, HC Hoppe, E Human, EJ Morris, Z Ngcete, L Oldfield, R Roth, A Shonhai, L Stephens, AI Louw (2008) Heterologous expression of plasmodial proteins for structural studies and functional annotation, Malaria J, 7, 197, Review. Impact factor 2.75. Highly accessesed status (>2000 times in < 6 months)

10. Birkholtz L, Clark K, Niemand J, van Brummelen T, Marechal E, Llinas M, Louw AI. (2008) Exploring functional genomics for drug target and therapeutics discovery in Plasmodia. Acta Tropica. 105, 113-123; epub 12 Nov 2007; Review. Impact factor 1.8

11. Clark K, Dhoogra M, AI Louw & L Birkholtz. (2008) Transcriptional responses of Plasmodium falciparum to alpha-difluoromethylornithine induced polyamine depletion. Biological Chemistry: 389, 111-125. Impact factor 2.57. Cited 2 times.

12. Williams M, Louw AI and Birkholtz L. (2007) Deletion of large areas in large Plasmodium falciparum genes: A comparative study. Malaria Journal, 6:64. Impact factor 2.75.

13. Burger P, Birkholtz L, Joubert F, Haider N, Walter RD, Louw AI. (2007) Structural and mechanistic insights into the action of Plasmodium falciparum spermidine synthase. Bioorg. Med. Chem 15, 1628–1637. Impact factor 2.29. Cited 5 times

14. Birkholtz L, Bastien O, Wells GA, Grando D, Joubert F, Kasam V, Zimmerman M, Ortet P, Jacq N, Saidani N, Roy S, Hofmann-Apitius M, Breton V, Louw AI, Marechal E. (2006) Integration and mining of malaria molecular, functional and pharmacological data: how far are we from a chemogenomic knowledge space? Malaria J, 5, 110, Review. Impact factor 2.75. Highly accessed status and one of top ten articles in 2007. Cited 6 times.

15. Wells G, Birkholtz L, Joubert F, Walter R, Louw AI. (2006) Novel properties of malarial S-adenosylmethionine decarboxylase as revealed by structural modelling, Journal of Molecular Graphics and Modelling, 24(4), 307-18. Impact factor 2.3. Cited 6 times.

16. Birkholtz LM, Wrenger C, Joubert F, Wells GA, Walter RD, Louw AI. (2004) Parasite-specific inserts in the bifunctional S-adenosylmethionine decarboxylase/ornithine decarboxylase of Plasmodium falciparum modulate catalytic activities and domain interactions. Biochem. J, 377, 439-448. Impact factor 4.2. Cited 14 times.

17. Birkholtz L, Joubert F, Neitz AW, Louw AI. (2003) Comparative properties of a three-dimensional model of Plasmodium falciparum ornithine decarboxylase, Proteins, 50, 464-473. Impact factor 4.6. Cited 6 times

18. Birkholtz L, Visser L, Brink A, Louw AI. (1998) Drug-resistant and mixed species malaria infections in Mpumalanga, South Africa, S. A. J. Sci. 94, 39-43 . Cited 1 time.

19. Birkholtz L, Visser L, Louw AI, van der Linde R, Brink AJ. (1998) The prevalence of mixed-species and anti-folate resistant malaria infections in Mpumalanga, S. A. Med. J. 88, 58-60. Impact factor 1.07. Cited 1 time.

 

Conference papers:

1.   Niemand J, Birkholtz L, Louw AI and K Kirk. Polyamine uptake in the malaria parasite, Plasmodium falciparum, is dependent on the parasites membrane potential. 2010 MALARIA J. 9 (Suppl 2), O24.

2.   Morris, E.J., Ngcete, Z., Birkholtz, L-M. and Louw, A.I. New Drugs to Fight Malaria. In Biovision 2008. From promises to practice: applications of science and technology in food, healthcare,energy and environment. Ed Ismail Serageldin, Ehsan Masood, with Mohamed El-Faham and Marwa El-Wakil. Alexandria, Egypt: Bibliotheca Alexandrina, 2010. pp229-234. ISBN 978-977-452-177-5.

3.   Birkholtz L, Williams M, Reeksting S, Wells G, Roux S, Walter RD and AI Louw. A unique bifunctional enzyme complex controlling polyamine biosynthesis in Plasmodium falciparum is regulated by parasite-specific inserts. International Journal of Parasitology, 2008, 38

4.   Van Brummelen AC, Llinas M, Louw AI and Birkholtz L. Co-inhibition of S-adenosylmethionine decarboxylase / ornithine decarboxylase of Plasmodium falciparum reveal compensatory mechanisms in the transcriptome. International Journal of Parasitology, 2008, 38

 

Published by Annel Smit

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