Scientific Challenges

 
Estimated incidence per 100,000 population (2008)
Source: World Health Organization
Confirmed multi-drug resistant TB cases (2008)
Source: World Health Organization
Estimated incidence (2007)
Source: World Health Organization
Estimated TB cases who are HIV-positive(2008)
Source: World Health Organization
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Using the tools of basic science, the KwaZulu-Natal Research Institute for Tuberculosis and HIV seeks new approaches to fighting these deadly diseases.

Scientific Opportunities

The Sigal, Pym, Ndung'u and Balagadde labs are looking for outstanding, innovative post doctoral research fellows.

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The Sigal lab is looking for outstanding Masters students with a background in biology, microbiology, biochemistry, virology, or engineering.

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Publications

Rapid sequencing of the Mycobacterium tuberculosis pncA gene for the detection of pyrazinamide susceptibility. - J Clin Microbiol. 2014 Aug 27. pii: JCM.02438-14. [Epub ahead of print]
Multidrug-resistant tuberculosis and culture conversion with bedaquiline. - N Engl J Med. 2014 Aug 21;371(8):723-32. doi: 10.1056/NEJMoa1313865.
The fitness landscape of HIV-1 gag: advanced modeling approaches and validation of model predictions by in vitro testing. - PLoS Comput Biol. 2014 Aug 7;10(8):e1003776. doi: 10.1371/journal.pcbi.1003776. eCollection 2014.
Comparison of Amplicor and GeneXpert MTB/RIF Tests for Diagnosis of Tuberculous Meningitis. - J Clin Microbiol. 2014 Oct;52(10):3777-80. doi: 10.1128/JCM.01235-14. Epub 2014 Jul 23.
Biological differences between the sexes and susceptibility to tuberculosis. - J Infect Dis. 2014 Jul 15;209 Suppl 3:S100-6. doi: 10.1093/infdis/jiu147.
HIV transmission. Selection bias at the heterosexual HIV-1 transmission bottleneck - Science. 2014 Jul 11;345(6193):1254031. doi: 10.1126/science.1254031. Epub 2014 Jul 10.
Selection of RNA aptamers against the M. tuberculosis EsxG protein using surface plasmon resonance-based SELEX. - Biochem Biophys Res Commun. 2014 Jun 20;449(1):114-9. doi: 10.1016/j.bbrc.2014.04.163. Epub 2014 May 9.
RNA and imidazoquinolines are sensed by distinct TLR7/8 ectodomain sites resulting in functionally disparate signaling events. - J Immunol. 2014 Jun 15;192(12):5963-73. doi: 10.4049/jimmunol.1303058. Epub 2014 May 9.
Effect of Female Genital Schistosomiasis and Anti-Schistosomal Treatment on Monocytes, CD4+ T-Cells and CCR5 in the Female Genital Tract. - PLoS One 2014 Jun 4;9(6):e98593. doi: 10.1371/journal.pone.0098593. eCollection 2014. PMID 24896815.
Consensus standards for introductory e-learning courses in human participants research ethics. - J Med Ethics. 2014 Jun;40(6):426-8. doi: 10.1136/medethics-2013-101572. Epub 2013 Aug 19.
HIV Subtype Influences HLA-B*07:02-Associated HIV Disease Outcome. - AIDS Res Hum Retroviruses. 2014 May;30(5):468-75. doi: 10.1089/AID.2013.0197. Epub 2013 Oct 4.
TRIM5α and TRIM22 are differentially regulated according to HIV-1 infection phase and compartment. - J Virol. 2014 Apr;88(8):4291-303. doi: 10.1128/JVI.03603-13. Epub 2014 Jan 29.
Regulatory T cells expanded from HIV-1-infected individuals maintain phenotype, TCR repertoire and suppressive capacity. - PLoS One. 2014 Feb 3;9(2):e86920. doi: 10.1371/journal.pone.0086920. eCollection 2014.
Neutrophil counts in persons of African origin. - Curr Opin Hematol. 2014 Jan;21(1):50-7. doi: 10.1097/MOH.0000000000000007.
Low levels of peripheral CD161++CD8+ Mucosal Associated Invariant T (MAIT) cells are found in HIV and HIV/TB co-infection - PLos ONE, 2013 Dec 31; 8(12):e83474. Doi: 10.1371/journal.pone.0083474. (PMID: 234391773)
Whole-genome sequencing to establish relapse or re-infection with Mycobacterium tuberculosis: a retrospective observational study. - Lancet Respir Med. 2013 Dec;1(10):786-92. doi: 10.1016/S2213-2600(13)70231-5. Epub 2013 Nov 21.
High-throughput sequencing enhanced phage display identifies peptides that bind mycobacteria. - PLoS One. 2013 Nov 12;8(11):e77844. doi: 10.1371/journal.pone.0077844. eCollection 2013.
S100A8/A9 proteins mediate neutrophilic inflammation and lung pathology during tuberculosis. - Am J Respir Crit Care Med. 2013 Nov 1;188(9):1137-46. doi: 10.1164/rccm.201304-0803OC.
Diagnostic accuracy of quantitative PCR (Xpert MTB/RIF) for tuberculous meningitis in a high burden setting: a prospective study. - PLoS Med. 2013 Oct;10(10):e1001536. doi: 10.1371/journal.pmed.1001536. Epub 2013 Oct 22
The intracellular sensor NOD2 induces microRNA-29 expression in human dendritic cells to limit IL-23 release. - Immunity. 2013 Sep 19;39(3):521-36. doi: 10.1016/j.immuni.2013.08.035.
Ability of HIV-1 Nef to downregulate CD4 and HLA class I differs among viral subtypes. - Retrovirology. 2013 Sep 16;10:100. doi: 10.1186/1742-4690-10-100.
Nef-specific CD8+ T cell responses contribute to HIV-1 immune control. - PLoS One. 2013 Sep 2;8(9):e73117. doi: 10.1371/journal.pone.0073117. eCollection 2013
Nef-specific CD8+ T cell responses contribute to HIV-1 immune control. - PLoS One. 2013 Sep 2;8(9):e73117. doi: 10.1371/journal.pone.0073117. eCollection 2013.
Clinical and mycological predictors of cryptococcosis-associated immune reconstitution inflammatory syndrome. - AIDS. 2013 Aug 24;27(13):2089-99. doi: 10.1097/QAD.0b013e3283614a8d.
Immunohistological characterization of spinal TB granulomas from HIV-negative and -positive patients. - Tuberculosis (Edinb). 2013 Jul;93(4):432-41. doi: 10.1016/j.tube.2013.02.009. Epub 2013 Mar 28.
Structure and interactions of the human programmed cell death 1 receptor. - J Biol Chem. 2013 Apr 26;288(17):11771-85. doi: 10.1074/jbc.M112.448126. Epub 2013 Feb 15.
EDCTP regional networks of excellence: initial merits for planned clinical trials in Africa. - BMC Public Health. 2013 Mar 22;13:258. doi: 10.1186/1471-2458-13-258.
Changes in Natural Killer cell activation and function during primary HIV-1 Infection. - PLoS One. 2013;8(1):e53251. doi: 10.1371/journal.pone.0053251. Epub 2013 Jan 9.
The Physiology and genetics of oxidative stress in mycobacteria - In: Molecular Genetics of Mycobacteria. 2nd edition 2013
Characterization of anti-HIV-1 neutralizing and binding antibodies in chronic HIV-1 subtype C infection. - Virology. 2012 Nov 25;433(2):410-20. doi: 10.1016/j.virol.2012.08.033. Epub 2012 Sep 18.
Co-operative additive effects between HLA alleles in control of HIV-1. - PLoS One. 2012;7(10):e47799. doi: 10.1371/journal.pone.0047799. Epub 2012 Oct 19.
Modeling early bactericidal activity in murine tuberculosis provides insights into the activity of isoniazid and pyrazinamide. - Proc Natl Acad Sci U S A. 2012 Sep 11;109(37):15001-5. doi: 10.1073/pnas.1203636109. Epub 2012 Aug 27.
Heme oxygenase-1 promotes granuloma development and protects against dissemination of mycobacteria. - Lab Invest. 2012 Nov;92(11):1541-52. doi: 10.1038/labinvest.2012.125. Epub 2012 Sep 10.
Modeling early bactericidal activity in murine tuberculosis provides insights into the activity of isoniazid and pyrazinamide. - Proc Natl Acad Sci U S A. 2012 Sep 11;109(37):15001-5. doi: 10.1073/pnas.1203636109. Epub 2012 Aug 27.
As Good As It Gets? The Problem of HIV Persistence despite Antiretroviral Drugs. - Cell Host Microbe. 2012 Aug 16;12(2):132-8. *Corresponding author.
New drugs for the treatment of tuberculosis: hope and reality. - Int J Tuberc Lung Dis. 2012 Aug;16(8):1005-14. doi: 10.5588/ijtld.12.0277.
Mycobacterium tuberculosis WhiB4 regulates oxidative stress response to modulate survival and dissemination in vivo. - Mol Microbiol. 2012 Sep;85(6):1148-65. doi: 10.1111/j.1365-2958.2012.08165.x. Epub 2012 Jul 26.
Environmental heme-based sensor proteins: implications for understanding bacterial pathogenesis. - Antioxid Redox Signal. 2012 Nov 1;17(9):1232-45. doi: 10.1089/ars.2012.4613. Epub 2012 Jun 13.
Iron sulfur cluster proteins and microbial regulation: implications for understanding tuberculosis. - Curr Opin Chem Biol. 2012 Apr;16(1-2):45-53. doi: 10.1016/j.cbpa.2012.03.004. Epub 2012 Apr 4.
Mycobacterium tuberculosis WhiB3: a novel iron-sulfur cluster protein that regulates redox homeostasis and virulence. - Antioxid Redox Signal. 2012 Apr 1;16(7):687-97. doi: 10.1089/ars.2011.4341.
Reduced antituberculosis drug concentrations in HIV-infected patients who are men or have low weight: implications for international dosing guidelines. - Antimicrob Agents Chemother. 2012 Jun;56(6):3232-8. doi: 10.1128/AAC.05526-11. Epub 2012 Mar 12.
Human MAIT and CD8αα cells develop from a pool of type-17 precommitted CD8+ T cells. - Blood. 2012 Jan 12;119(2):422-33. doi: 10.1182/blood-2011-05-353789. Epub 2011 Nov 15.
Redox homeostasis in mycobacteria: the key to tuberculosis control? - Expert Rev Mol Med. 2011 Dec 16;13:e39. doi: 10.1017/S1462399411002079.
International Spread of MDR TB from Tugela Ferry, South Africa - Emerg Infect Dis. 2011 Nov;17(11):2035-7. doi: 10.3201/eid1711.110291.
In silico children and the glass mouse model - Antimicrob Agents Chemother. 2011 Feb
The new role of the microchemostat in the bioengineering revolution - 31st Annual International Conference of the IEEE Engineering in Medicine and Biology Society
Intersubtype differences in the effect of a rare p24 gag mutation on HIV-1 replicative fitness. - J Virol. 2012 Dec;86(24):13423-33. doi: 10.1128/JVI.02171-12. Epub 2012 Sep 26.
HIV control through a single nucleotide on the HLA-B locus. - J Virol. 2012 Nov;86(21):11493-500. doi: 10.1128/JVI.01020-12. Epub 2012 Aug 15.
September 30, 2014

K-RITH has teamed up with Neotel and IBM to significantly increase its Information and Communications Technology (ICT) and broadband services.  The project will see the implementation of a fully comprehensive ICT disaster recovery plan and supporting infrastructure, which includes the establishment of a physical disaster recovery environment in Neotel’s data centre in Midrand, Gauteng.

September 30, 2014

K-RITH Investigator Adrie Steyn and post-doctoral research fellows Dirk Lamprecht and Adam Yadon presented at the 2nd H3-D Symposium that took place in Zambia from 27-29 August 2014.  Drug discovery scientists and clinicians all working on drugs to combat TB infection attended the conference from Africa and across the globe.

September 30, 2014

K-RITH Assistant Investigator, Dr. Alex Sigal has initiated a rolling part-time, paid work experience programme for current undergraduate science students.  The students, who have to apply for the position and undergo a rigorous selection process are actively involved in the work of his lab at K-RITH and are required to perform useful laboratory tasks.

September 30, 2014

Suzanne Cory is one of Australia’s most distinguished molecular biologists.

September 30, 2014

Research Associate, Emily Wong, won best Staff Oral Presentation at the UKZN College of Health Sciences Research Symposium that took place at the  K-RITH Tower Building earlier this month.  Emily, who has recently been awarded a Post-doctoral Fellowship in Tropical Infectious Diseases by the Burroughs Wellcome Fund/American Society of Tropical Medicine and Hygiene, was one of 17 other K-RITH researchers who attended the two-day Symposium.

September 22, 2014

Associate Professor, Muazzam Jacobs, will speak on 'Tumour Necrosis Factor Receptor (TNF-TNFR) interaction - a critical requirement for host immune protection against Mycobacterium tuberculosis infection' for the September K-RITH Seminar Series.

August 29, 2014

Professor Lynn Morris, Chief Specialist Scientist and head of the HIV Virology laboratories within the Centre of HIV & STI’s at NICD will be speaking on 'Prospects for an antibody-based HIV vaccine' at the August K-RITH Seminar.

August 5, 2014

Dr. Shalek will be delivering  a talk on ‘Micro & Nanoscale Strategies for Systems Biology: Lessons From Immune Cells’.

July 29, 2014

Professor of Medicine at Portland Medical Centre, Dr. David Lewinsohn will be delivering  a talk on ‘Pathogen Reactive Human MAITs’.