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Biotechnol. J. 2008, 3, 1351–1354 DOI 10.1002/biot.200800231 www.biotechnology-journal.com

Company profile

The Centre for Proteomic and Genomic Research(CPGR) in Cape Town, South Africa, is a world-class technology centre funded by the Cape BiotechTrust and PlantBio, two of the government’s pre-mier instruments for stimulating growth of thebiotech sector.The CPGR was founded in 2006 as anon-profit organisation that focuses on high-throughput integrated research in the genomic andproteomic arena. Today the CPGR runs projects inthe biomedical field with relevance to diagnosticsresearch and drug discovery in human diseasessuch as tuberculosis, HIV/AIDS, malaria and can-cers. Increasingly, the CPGR is also involved inplant biotechnology research and in food safety.

The CPGR provides access to state-of-the-arttechnology platforms for a variety of genomic andproteomic research applications and uses theseplatforms in collaborations with scientists in aca-demia and industry, both locally and worldwide. Itsstaff members are engaged in diverse projects,ranging from mass spectrometry-based workflowsfor discovering novel disease biomarkers to mi-croarray-based studies for serum profiling and de-veloping new diagnostic tools for malaria, HIV andtuberculosis (TB).

The CPGR was established with a vision ofhelping to increase the South African research out-

put and knowledge base, while becoming financial-ly sustainable through providing services and col-laborative projects. To date, scientists at the CPGRwork with > 80 different researchers, groups, uni-versities and companies, across a number of sec-tors. Many of the collaborative projects focus onimproving diagnoses and therapies for infectiousdiseases, as part of the long-term aims of the CPGRto benefit the communities in South Africa. Some ofthe current studies include the search for new, im-proved, molecular diagnostic and prognostic mark-ers of diseases such as TB, malaria, leukaemia andcolorectal cancer; the search for markers of patho-gen resistance in maize; an assessment of the pos-sible health risks associated with the developmentof genetically modified plants; and the improve-ment of yeast strains for use in the wine biotech-nology sector. These diverse projects are largelycarried out using automated platforms for highthroughput processing of microarrays and pro-teomics-based workflows.

“We need to use automated systems to minimiseour manual procedures and assay costs as far aspossible, while at the same time increasing thequality of our results,” explained Dr ReinhardHiller, Managing Director of the CPGR. “We arenow fully equipped for processing almost all exist-ing slide-based microarray formats, including ge-nomic DNA, microRNA and protein microarrays.We have also established facilities for RT-PCR-based gene expression profiling, genotyping, andstate-of-the-art mass spectrometry-based differ-ential proteomics. In addition, we are also anAffymetrix-accredited service provider and are theonly facility in Southern Africa that is trained to useall Affymetrix Genechip® products, including the

Company Profile

Integrating high throughput technologies to advance genomicand proteomic research in South Africa

Reinhard Hiller1 and Jonathan M. Blackburn1,2

1 Centre for Proteomic and Genomic Research, Cape Town, South Africa2 Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa

Correspondence: Dr. Reinhard Hiller, Centre for Proteomic and GenomicResearch, c/o Institute of Infectious Disease and Molecular Medicine,Faculty of Health Sciences, University of Cape Town, Observatory,Cape Town 7925, South AfricaE-mail: reinhard.hiller@cpgr.org.zaFax: +27-21-650-4833

Received 25 September 2008Accepted 1 October 2008

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latest SNP6.0 genotyping arrays that can be used todetermine the presence of 1 million human SNPsin a single experiment.”

Identifying gene expression changes ininfectious diseases

Scientists at the CPGR have recently completed anumber of optimisation studies using DNA, RNA,protein and cytokine arrays from diverse sourcesand, together with collaborators, are now involvedin many microarray-based research projects to in-vestigate gene expression changes in patients withinfectious diseases such as tuberculosis, HIV andmalaria.

The slide-based microarray platform includes afully automated hybridisation station (Tecan HS4800™ Pro) for the simultaneous processing of upto 12 microarray slides in single, dual or quadchamber compliant array formats, as well as a high-resolution, automated microarray scanner (TecanLS Reloaded™), and a Genetix QArray2 microarrayprinter (Genetix) for custom array printing. TheQuadChamber™ enables simultaneous processingof four individual, high-density microarrays print-ed on a single glass slide, using the HS 4800 Pro,with no cross-contamination between the arrays.

“We chose the HS 4800 Pro for automated mi-croarray processing based on previous experiencewith this and other systems; it is really versatile,”Rachel van Dyk, microarray specialist at the CPGRsaid. “The system performs all steps of the hybridi-sation process, from pre-hybridisation through todrying, of single, dual and even quadruplex mi-croarrays.”

“We are also involved in using a number of cus-tom protein and peptide microarray assays, for ex-ample for allergy diagnosis or infectious diseaseresearch,” Rachel continued.“One example is a col-laborative project using high-density TB peptidearrays developed by JPT (JPT Peptide Technolo-gies) to screen for potential diagnostic antibodiesfor TB. New, reliable, simple and quick tests are ur-gently needed for TB diagnosis, which is particu-larly difficult to diagnose in children with HIV.”

“We are also using protein microarrays devel-oped by VBC-GENOMICS for the diagnosis of al-lergic diseases. These diagnostic arrays containhundreds of allergen molecules immobilised infour identical microarrays on a single microscopyslide. While originally designed for manual pro-cessing, we are now adapting these miniaturisedantibody-capturing assays to a 4-plex and 16-plexformat using the HS 4800 Pro and the TecanHydroFlex™, respectively, which will enable us to

increase assay throughput and quality, while sig-nificantly reducing the costs per data-point.”

Currently, CPGR scientists are developing auto-mated protocols for processing Gentel’s (GentelBiosciences) multiplex biomarker arrays. “Thesemultiplex profiling assays are important for re-search in many disease areas, such as cancer or in-fectious diseases” Rachel explained.“To give an ex-

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ample, highly automated cytokine profiling assaysare very important in the context of monitoringclinical trials, where the consistency of results is akey prerequisite. However, using these cytokine ar-rays is only the first step towards implementingother multiplexed antibody capturing and sand-wich antibody assays that come in 8- or 16-plex for-mats.” In the case of the 16-plex protein microarrayslides, automated incubation and washing is cur-rently carried out at the CPGR using a HydroFlexautomated microplate washing, filtration and sep-aration system, which was customised by Tecan forthis purpose.

Identifying disease biomarkers for crops andhumans

The CPGR also runs a proteomics platform for usein applications such as mass spectrometry-basedprotein characterisation, peptide mass fingerprint-ing, de novo sequencing of proteins and, in particu-lar, comparative protein expression profiling inbiomedical and agricultural research studies. Theset-up includes a 4800 MALDI TOF/TOF™ Analyz-er (Applied Biosystems) and an Ultimate™ 3000Nano LC system (Dionex Corporation).

The proteomics platform is used in diverse proj-ects, including differential expression profiling ofsamples from people with diseases such as cancers,TB, HIV and autoimmune diseases. A similar ap-proach is now being used at the CPGR for compar-ative expression profiling of natural and genetical-ly modified plants.

“We are also becoming involved now in a num-ber of bioprospecting projects,” said Prof. JonathanBlackburn, Research Director at the CPGR. “Thereis increasing interest here in studying the possiblebiomedical applications of indigenous plants andof other biological sources. For example, in marinebioprospecting we are planning to look for new

drug activity in certain seawater species by frac-tionating samples and then adding them to bloodcell cultures to look for activity patterns. We canthen pick out any active fractions and use massspectrometry to identify the key molecules in-volved in the activity, and even go on to use our mi-croarray technologies to validate candidate activeproteins and to determine the mechanism of actionof anything interesting we find.”

Another area of research at the CPGR is the de-velopment of pathogen detection assays for grapes.The grapevine biotech industry plays a major rolein South Africa, and there is great interest in devel-oping or improving assays for detecting pathogensthat affect grapes and vine growth. “We plan to usemass spectrometry to identify proteins that are rel-evant for diagnostic purposes in these pathogens,and then we intend to develop multiplex pathogendetection assays using our BioPlex (Bio-Rad Labo-ratories) platform,” Dr. Shane Murray, a plant ex-pert at the CPGR, explained.

“The versatility and ability to integrate our plat-forms is essential to many of our workflows, mak-ing it possible for us to switch easily between, forexample, HPLC separation, microarray develop-ment and mass spectrometry-based applications ina variety of different studies.” Prof Blackburn con-tinued. “We have also recently added an automatedliquid handling workstation (Tecan Freedom EVO®)to our collection and, amongst other applications,this workstation will be used for automated DNAand RNA extraction, for the preparation of serumsamples for multiplex immunoassays on our Lu-minex platform, for the parallel depletion of sam-ples subjected to mass spectrometry analysis, andfor all the liquid handling needed to prepare 384-well plates for our RT-PCR platform.”

“This liquid handling platform will be particu-larly useful in our genotyping studies, looking forSNPs and biomarkers of diseases of the immunesystem, infectious diseases, cancer, asthma, allergy,

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autoimmune diseases and parasites. We also planto use this platform for a plant biosafety and aller-genicity testing project and, eventually, for cell cul-

ture screening. This is another step towards turn-ing our laboratory into a high-throughput microar-ray and biomarker analysis platform,” ReinhardHiller concluded.“Moreover, we plan to use the liq-uid handling platform in large-scale biomarkerprofiling studies, making use of multiplex bead as-says on our BioPlex platform, to increase thethroughput in clinical trials and information-richdrug screening projects.

Prof. Jonathan Blackburn currently

holds a South African Research Chair in

Applied Proteomics & Chemical Biolo-

gy at the Institute of Infectious Disease

& Molecular Medicine, University of

Cape Town. He is co-founder and Re-

search Director of the CPGR, a member

of the UK GlyoArrays consortium

(www.glycoarrays.org.uk), and has re-

cently co-founded a US Biotech compa-

ny, Serametrix Inc (www.serametrix.com).

Previously, he held a prestigious Royal Society University Research

Fellowship in the Department of Biochemistry, Cambridge University

and co-founded a UK biotech company, Sense Proteomic Ltd, to com-

mercialize the protein function microarray technology invented in his

academic group. He acted as Chief Scientific Officer of that company

until a takeover by Procognia Ltd in 2002, after which he became the

Chief Scientist of the merged organisation, a post he held until early

2006.

He holds undergraduate and doctoral degrees in Chemistry from

the University of Oxford, is the inventor on 9 granted patents and 11

pending patents, and has published much innovative research in lead-

ing scientific journals.

Dr. Reinhard Hiller received a PhD in

Molecular Biology from the University

of Vienna, Austria (Inst. of Genetics &

Microbiology) in 2000 and an extramu-

ral Master Practitioner diploma in NLP

(Neurolinguistic Programming) in

2002. After completing his PhD he

joined a start-up biotech company

(VBC-GENOMICS) in Vienna, Austria,

where he developed the first protein

biochip-based test for allergic diseases, approved and marketed for

routine diagnostic purposes in Europe 4 years later. In 2005, he moved

to South Africa where he co-founded the Centre for Proteomic & Ge-

nomic Research (CPGR). As Managing Director of the CPGR Reinhard

dedicates his expertise and time to support and stimulate cutting-edge

research initiatives and new entrepreneurial ventures conducive to cre-

ating a strong biotech sector in South Africa.

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