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Division of MOLECULAR BIOLOGY and HUMAN GENETICS DEPARTMENT OF BIOMEDICAL SCIENCES
INTRODUCTION The Division of Molecular Biology and Human Genetics is a research unit focused on two main research fields namely tuberculosis TB and inherited genetic disorders These two apparently different fields are united through study of the fundamental biology of nucleic acids and genetic material of both humans and the bacteria This molecular approach to research is enhanced through the use of modern laboratory techniques and collaboration with numerous national and international leaders in these fields The division is supported and funded by amongst others the MRC DST and NRF through two centres namely the DST NRF Centre for Excellence in Biomedical TB Research CBTBR and the MRC Centre for Tuberculosis Research Molecular Biology We currently occupy a position bridging the gap between basic research and its application in clinical TB research and management This laboratory is engaged in fundamental research towards a better understanding of the biology of the bacterium which enables it to avoid destruction in the host and spread rapidly within human populations It is also at the cutting edge of research to identify novel bacterial and host markers that will considerably shorten the time taken to evaluate new drugs and vaccines and to develop new diagnostic tools and new multidisciplinary approaches for understanding the epidemiology of the disease Some of these efforts have broader applications most notably in areas such as wildlife management and veterinary disease Human Genetics The Division has an active research program in the field of human molecular genetics The main focus is to identify molecular mechanisms and the genetic aetiology underlying various disorders in local populations Current research projects are on Parkinson s disease human genetic susceptibility to TB and Post traumatic stress and anxiety disorders The Division has an active Clinical Genetics and Genetic Counselling group We provide genetic services in Tygerberg Hospital and a private outpatient service in the Faculty Research interests include clinical public health and qualitative research on foetal alcohol syndrome Down syndrome and primary immunodeficiencies 2 DEGREES OFFERED We offer a number of postgraduate degrees including BScHons in Molecular Biology BScHons in Human Genetics MSc in Molecular Biology MSc in Human Genetics PhD in Molecular Biology PhD in Human Genetics MMed in Clinical Genetics for medical registrars in Clinical Genetics The Honours BSc programs are structured to allow active participation in a research project At the same time a series of lectures and meetings covers current aspects of molecular and cellular biology and biotechnology Applications are considered from graduates with a BSc degree with majors in Genetics Biochemistry Pharmacology Microbiology Biotechnology etc minimum grade of 60 is required Applicants with a MB ChB are also eligible The MSc and PhD programs are entirely research based and students from various backgrounds e g Genetics Biochemistry Pharmacology Microbiology Physiology or Biotechnology are eligible for consideration CAREER OPPORTUNITIES Our degrees will equip students with various skills in molecular biology for a wide range of career opportunities including Diagnostic or research laboratories Representative for pharmaceutical or biotechnology companies Academia teaching Patenting and commercialisation of research outputs 3
INTRODUCTION The Division of Molecular Biology and Human Genetics is a research unit focused on two main research fields namely tuberculosis TB and inherited genetic disorders These two apparently different fields are united through study of the fundamental biology of nucleic acids and genetic material of both humans and the bacteria This molecular approach to research is enhanced through the use of modern laboratory techniques and collaboration with numerous national and international leaders in these fields The division is supported and funded by amongst others the MRC DST and NRF through two centres namely the DST NRF Centre for Excellence in Biomedical TB Research CBTBR and the MRC Centre for Tuberculosis Research Molecular Biology We currently occupy a position bridging the gap between basic research and its application in clinical TB research and management This laboratory is engaged in fundamental research towards a better understanding of the biology of the bacterium which enables it to avoid destruction in the host and spread rapidly within human populations It is also at the cutting edge of research to identify novel bacterial and host markers that will considerably shorten the time taken to evaluate new drugs and vaccines and to develop new diagnostic tools and new multidisciplinary approaches for understanding the epidemiology of the disease Some of these efforts have broader applications most notably in areas such as wildlife management and veterinary disease Human Genetics The Division has an active research program in the field of human molecular genetics The main focus is to identify molecular mechanisms and the genetic aetiology underlying various disorders in local populations Current research projects are on Parkinson s disease human genetic susceptibility to TB and Post traumatic stress and anxiety disorders The Division has an active Clinical Genetics and Genetic Counselling group We provide genetic services in Tygerberg Hospital and a private outpatient service in the Faculty Research interests include clinical public health and qualitative research on foetal alcohol syndrome Down syndrome and primary immunodeficiencies 2 DEGREES OFFERED We offer a number of postgraduate degrees including BScHons in Molecular Biology BScHons in Human Genetics MSc in Molecular Biology MSc in Human Genetics PhD in Molecular Biology PhD in Human Genetics MMed in Clinical Genetics for medical registrars in Clinical Genetics The Honours BSc programs are structured to allow active participation in a research project At the same time a series of lectures and meetings covers current aspects of molecular and cellular biology and biotechnology Applications are considered from graduates with a BSc degree with majors in Genetics Biochemistry Pharmacology Microbiology Biotechnology etc minimum grade of 60 is required Applicants with a MB ChB are also eligible The MSc and PhD programs are entirely research based and students from various backgrounds e g Genetics Biochemistry Pharmacology Microbiology Physiology or Biotechnology are eligible for consideration CAREER OPPORTUNITIES Our degrees will equip students with various skills in molecular biology for a wide range of career opportunities including Diagnostic or research laboratories Representative for pharmaceutical or biotechnology companies Academia teaching Patenting and commercialisation of research outputs 3
OUR CURRENT RESEARCH INTERESTS Molecular Biology Mycobactomics The overarching research aim of the Mycobactomics group is to exploit advanced omics technologies including second generation whole genome sequencing transcriptomics and proteomics informed by bioinformatics to perform in depth characterization of clinical strains of Mycobacterium tuberculosis M tb and other mycobacterial species isolated from humans and animals on the African continent Our research focuses on the evolution of the mycobacteria and of mycobacterial pathogenicity and drug resistance Molecular Epidemiology M tb strains from patients from different settings in South Africa are genetically characterized using techniques based on the transposition element IS6110 and other probes Using this genotypic data together with clinical data it has been possible to show that the epidemic is driven by transmission of many different strains transmission occurs outside of the household and recurrence occurs through reinfection Our Centre houses one of the largest collections of clinical isolates of drug susceptible and drug resistant TB Drug resistance Drug resistant TB especially MDR and XDR TB poses a threat to the success of TB control programmes and places an enormous financial burden on the health budget We are currently building a genome sequence bank comprising thousands of sequences of local clinical isolates These sequences allow us to scrutinize the local epidemic in terms of outbreak investigations within patient evolution of drug resistance transmission and discovering novel drug resistance causing mutations By combining Whole genome sequencing WGS with RNA seq or proteomics were are able to determine the impact of drug resistance on the physiology of M tb 4 Mycobacterial physiology drug target identification and drug testing We focus on the mycobacterial genes and metabolic pathways critical to the survival of M tb within the host We seek to understand their regulation and biology and assist chemists in the design and testing of inhibitors with the aim of developing novel anti TB drugs Another major thrust is to identify host factors involved in the survival of mycobacteria in mouse and human macrophages employing transcriptomics and proteomics We then investigate these targets in animal infection models with the long term aim of developing novel host directed therapeutics for tuberculosis Immunology Our main focus is the identification of immune biomarkers for use in trials for novel diagnostics new treatment regimens and vaccines We work with several international consortia and with several US European and African partners on large cohorts of participants searching for biomarkers of TB infection and disease We also focus on immune endocrine interactions and particularly the role of Type 2 Diabetes Mellitus in TB susceptibility Our laboratory team processes a range of sample types from participants including serum urine saliva sputum exhaled breath condensate bronchoalveolar lavage pleural fluid and cerebrospinal fluid http www sun ac za molbiogen index php en immunology home Animal tuberculosis TB is not found only in humans and animal species ranging from elephants to fish can also be affected Such diseases may be endemic or alien to an ecosystem and can affect that ecosystem Part of our research investigates not only TB in multiple animal species and ecosystems but also the variety of organisms related to the human form of TB that can cause TB like disease Such work is important to agriculture and conservation 5
OUR CURRENT RESEARCH INTERESTS Molecular Biology Mycobactomics The overarching research aim of the Mycobactomics group is to exploit advanced omics technologies including second generation whole genome sequencing transcriptomics and proteomics informed by bioinformatics to perform in depth characterization of clinical strains of Mycobacterium tuberculosis M tb and other mycobacterial species isolated from humans and animals on the African continent Our research focuses on the evolution of the mycobacteria and of mycobacterial pathogenicity and drug resistance Molecular Epidemiology M tb strains from patients from different settings in South Africa are genetically characterized using techniques based on the transposition element IS6110 and other probes Using this genotypic data together with clinical data it has been possible to show that the epidemic is driven by transmission of many different strains transmission occurs outside of the household and recurrence occurs through reinfection Our Centre houses one of the largest collections of clinical isolates of drug susceptible and drug resistant TB Drug resistance Drug resistant TB especially MDR and XDR TB poses a threat to the success of TB control programmes and places an enormous financial burden on the health budget We are currently building a genome sequence bank comprising thousands of sequences of local clinical isolates These sequences allow us to scrutinize the local epidemic in terms of outbreak investigations within patient evolution of drug resistance transmission and discovering novel drug resistance causing mutations By combining Whole genome sequencing WGS with RNA seq or proteomics were are able to determine the impact of drug resistance on the physiology of M tb 4 Mycobacterial physiology drug target identification and drug testing We focus on the mycobacterial genes and metabolic pathways critical to the survival of M tb within the host We seek to understand their regulation and biology and assist chemists in the design and testing of inhibitors with the aim of developing novel anti TB drugs Another major thrust is to identify host factors involved in the survival of mycobacteria in mouse and human macrophages employing transcriptomics and proteomics We then investigate these targets in animal infection models with the long term aim of developing novel host directed therapeutics for tuberculosis Immunology Our main focus is the identification of immune biomarkers for use in trials for novel diagnostics new treatment regimens and vaccines We work with several international consortia and with several US European and African partners on large cohorts of participants searching for biomarkers of TB infection and disease We also focus on immune endocrine interactions and particularly the role of Type 2 Diabetes Mellitus in TB susceptibility Our laboratory team processes a range of sample types from participants including serum urine saliva sputum exhaled breath condensate bronchoalveolar lavage pleural fluid and cerebrospinal fluid http www sun ac za molbiogen index php en immunology home Animal tuberculosis TB is not found only in humans and animal species ranging from elephants to fish can also be affected Such diseases may be endemic or alien to an ecosystem and can affect that ecosystem Part of our research investigates not only TB in multiple animal species and ecosystems but also the variety of organisms related to the human form of TB that can cause TB like disease Such work is important to agriculture and conservation 5
OUR CURRENT RESEARCH INTERESTS Human Genetics Genetic aetiology of Parkinson s disease PD Over the past two decades this relatively common and debilitating neurodegenerative disorder has been shown to have a significant genetic component with a number of causative genes being identified Our research is focused on identifying the genetic causes of PD in South African patients using various mutation screening and cutting edge next generation sequencing approaches Another research focus is to investigate disease mechanisms leading to neuronal death www sun ac za parkinsons Molecular mechanisms of Post traumatic Stress Disorder PTSD PTSD is a prevalent and severe anxiety disorder that significantly impairs normal functioning To date very few of the molecular mechanisms underlying the disorder have been elucidated We aim to identify possible molecular markers that increase susceptibility to developing PTSD A number of studies are underway including protein protein interactions and gene expression and epigenetic analyses to facilitate the identification of such molecular markers Fetal alcohol spectrum disorder FasD The Clinical Genetics and Genetic Counseling group partners with the Foundation for Alcohol Related Research FARR to conduct research on surveillance and prevention of FASD in South Africa Human genetic susceptibility to tuberculosis Although 1 3rd of the world s population is infected with M tb the vast majority of these persons will never develop any clinical disease In the 10 who progress to active disease inter individual variation in the 6 immune response plays a major role in determining the disease outcomes and our focus is on identifying the genes involved We aim to identify unknown host genetic factors influencing TB immunity by studying the complete susceptibility spectrum ranging from individuals with rare susceptibility mutations to common genetic variants in the general population We also take the work to the cellular level by studying the function of the genes discovered Bioinformatics As biomedical research in South Africa has become increasingly reliant on molecular biotechnologies the volume of data produced has grown considerably The bioinformatics group was created as a trans disciplinary team in response to this need It comprises a diverse group of experienced researchers and students who collaborate with the various other teams on joint projects contributing and providing training in skills such as statistical genetics proteomics data management and processing programming and biostatistics In this way we aim to maximise the potential of data generated locally and transfer much needed skills to a new generation of scientists Molecular Biology and Human Genetics Clinical Studies The clinical team of the division works actively on observation studies and clinical trials concerning tuberculosis HIV Diabetes and parasites The team conduct routine and special investigations including bronchoscopies and PET CT s They also recruit volunteers and gather valuable data and specimen used for fundamental and translational research and new diagnostic discovery The scale of the projects range from post graduate student level to large international consortia 7
OUR CURRENT RESEARCH INTERESTS Human Genetics Genetic aetiology of Parkinson s disease PD Over the past two decades this relatively common and debilitating neurodegenerative disorder has been shown to have a significant genetic component with a number of causative genes being identified Our research is focused on identifying the genetic causes of PD in South African patients using various mutation screening and cutting edge next generation sequencing approaches Another research focus is to investigate disease mechanisms leading to neuronal death www sun ac za parkinsons Molecular mechanisms of Post traumatic Stress Disorder PTSD PTSD is a prevalent and severe anxiety disorder that significantly impairs normal functioning To date very few of the molecular mechanisms underlying the disorder have been elucidated We aim to identify possible molecular markers that increase susceptibility to developing PTSD A number of studies are underway including protein protein interactions and gene expression and epigenetic analyses to facilitate the identification of such molecular markers Fetal alcohol spectrum disorder FasD The Clinical Genetics and Genetic Counseling group partners with the Foundation for Alcohol Related Research FARR to conduct research on surveillance and prevention of FASD in South Africa Human genetic susceptibility to tuberculosis Although 1 3rd of the world s population is infected with M tb the vast majority of these persons will never develop any clinical disease In the 10 who progress to active disease inter individual variation in the 6 immune response plays a major role in determining the disease outcomes and our focus is on identifying the genes involved We aim to identify unknown host genetic factors influencing TB immunity by studying the complete susceptibility spectrum ranging from individuals with rare susceptibility mutations to common genetic variants in the general population We also take the work to the cellular level by studying the function of the genes discovered Bioinformatics As biomedical research in South Africa has become increasingly reliant on molecular biotechnologies the volume of data produced has grown considerably The bioinformatics group was created as a trans disciplinary team in response to this need It comprises a diverse group of experienced researchers and students who collaborate with the various other teams on joint projects contributing and providing training in skills such as statistical genetics proteomics data management and processing programming and biostatistics In this way we aim to maximise the potential of data generated locally and transfer much needed skills to a new generation of scientists Molecular Biology and Human Genetics Clinical Studies The clinical team of the division works actively on observation studies and clinical trials concerning tuberculosis HIV Diabetes and parasites The team conduct routine and special investigations including bronchoscopies and PET CT s They also recruit volunteers and gather valuable data and specimen used for fundamental and translational research and new diagnostic discovery The scale of the projects range from post graduate student level to large international consortia 7
CONTACT DETAILS SUN MeDIA Head Prof Gerhard Walzl gwalzl sun ac za 021 938 9401 021 938 9124 BScHons Molecular Biology Dr Jennifer Jackson jacksonj sun ac za 021 938 9069 BScHons Human Genetics Dr Marlo Moller marlom sun ac za 021 938 9694 MSc and PhD Ms Glenda Durrheim gad sun ac za 021 938 9696 Animal tuberculosis Prof Michele Miller Dr Sven Parsons miller sun ac za sparsons sun ac za 021 938 9948 Bioinformatics Prof Gerard Tromp Prof David Tabb Prof Gian van der Spuy gctromp sun ac za dtabb sun ac za gvds sun ac za 021 938 9947 021 938 9049 021 938 9412 Clinical mycobacteriology and epidemiology Prof Grant Theron gtheron sun ac za 021 938 9693 Drug targets and testing Prof Ian Wiid Dr Bienyameen Baker Prof Dr Colin Kenyon iw sun ac za brubaker sun ac za kenyon sun ac za 021 938 9475 021 938 9402 021 938 9950 Fetal alcohol spectrum disorder FASD Dr Mike Urban urban sun ac za 021 938 9806 Genetic aetiology of Parkinson s disease PD Prof Soraya Bardien sbardien sun ac za 021 938 9681 Host pathogen interactions Prof Samantha Sampson samantha sampson sun ac za 021 938 9951 Human genetic susceptibility to tuberculosis Prof Eileen Hoal Dr Craig Kinnear Dr Marlo M ller egvh sun ac za gkin sun ac za marlom sun ac za 021 938 9412 021 938 9695 021 938 9694 Immunology Prof Gerhard Walzl gwalzl sun ac za 021 938 9401 Molecular Biology and Human Genetics clinical studies Dr Fanie Malherbe malherbe sun ac za 021 938 9639 Molecular epidemiology and drug resistance Prof Rob Warren Dr Elizma Streicher rw1 sun ac za lizma sun ac za 021 938 9251 021 938 9073 Mycobactomics Prof Rob Warren Prof Samantha Sampson rw1 sun ac za samantha sampson sun ac za 021 938 9251 021 938 9951 Mycobacterial physiology Dr Monique Williams moniquejw sun ac za 021 938 9073 DEGREES OFFERED RESEARCH AREAS http www sun ac za english faculty healthsciences Molecular_Biology_Human_Genetics Physical address Fisan Building 4th Floor Francie van Zijl Drive Faculty of Medicine and Health Sciences 8 Tygerberg
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