Leslie

Alasdair Leslie, D.Phil, MSc, BSC

Lab Info:

Principal Investigator: Alasdair Leslie, D.Phil, MSc, BSC

Office/Location: K-RITH

Phone: +27 31 260 4991 Ext 4186

Email: al.leslie@k-rith.org

Category: Associate Members

When Alasdair Leslie left Africa in 2002 to return to his native England, it wasn’t to do science—that’s just how things turned out. But ten years later, he is returning to the sub-equatorial continent with a clear scientific purpose: he wants to understand exactly how human cells respond to infection with HIV and tuberculosis.

 
Leslie arrived in Malawi in 1997 as a volunteer with the United Kingdom’s Voluntary Service Overseas program. After teaching for two years at Kasungu Secondary School, he remained in the country to work with local farmers. That work followed naturally on the agricultural master’s degree Leslie had earned at the University of Bath, and when he returned to England a few years later, accompanying the woman who would soon become his wife, he expected to continue along a similar path.

 
But Leslie’s prospects in agriculture in the UK didn’t pan out, and he needed a job. Broadening his search, he came across an ad from a lab devoted to studying the immune response to HIV infection. He recognized an opportunity to work on a problem whose devastating effects had been painfully apparent in Malawi, where high rates of HIV infection are compounded by extreme poverty and a lack of health care infrastructure. Leslie recalls losing several friends to the disease during his time there. “At least, we assumed that’s what it was. It wasn’t really talked about,” he says.

 
Leslie took the job as a research assistant at Oxford University, and within six months, the head of the lab had offered him a position as a Ph.D. student. Since then, he has devoted his studies to understanding the relationship between HIV and its host, focusing on immune cells’ earliest response to the pathogen. Recently, he’s expanded those studies to include the tuberculosis-causing bacteria Mycobacterium tuberculosis (mTB).

 
He returned to Africa in 2012 with deliberate plans to advance that work. K-RITH, he will pursue two main strategies for understanding HIV and TB.

 

Research Interests

  • Innate Immune Response
  • Neutrophils
  • Innate Lymphoid Cells

 
Innate immune cells are among the first to encounter invading pathogens, and the outcome of this interaction is a key factor in the subsequent course of infection. However, despite over 25 years of research in HIV and perhaps over a century for TB, there is still much about the innate immune response to both pathogens that remains unclear. This knowledge gap is partly due to the fact that some aspects of the innate response are hard to study. Neutrophils for example, which are increasingly thought to be central in the immune response to both HIV and TB, must be worked on fresh and cannot be frozen down for investigation at a later time or in a different location. In addition, some of the most important interactions between innate immune cells and these pathogens occur in the tissue and not in peripheral blood, which by necessity is the compartment on which most HIV and TB research is based. Fortunately, as a cutting edge research institute at the very heart of the HIV and TB co-epidemic, we are ideally placed to overcome these challenges and improve our understanding of the innate immune response to HIV, TB and their co-infection. In so doing we seek to learn how these responses might be exploited to improve the treatment and diagnosis of these deadly diseases.

 

Significant Publications

1. The hypervariable HIV-1 capsid protein residues comprise HLA-driven CD8+ T-cell escape mutations and covarying HLA-independent polymorphisms. J Virol. 2010 Nov 24. [Epub ahead of print]

 
2. HLA-Cw*03 -restricted CD8+ T-cell responses targeting the HIV-1 Gag Major Homology Region drive virus immune escape and fitness constraints compensated by intra-codon variation. J Virol. 2010 Nov;84(21):11279-88.

 
3. Additive Contribution of HLA Class I Alleles in the Immune Control of HIV-1 Infection. J Virol. 2010 Oct;84(19):9879-88

 
4. E.Evolution of HLA-B*5703 HIV-1 escape mutations in HLA- B*5703-positive individuals and their transmission recipients. J Exp Med. 2009 Apr 13;206(4):909-21.

 
5. HLA footprints on human immunodeficiency virus type 1 are associated with interclade polymorphisms and intraclade phylogenetic clustering. J Virol. 2009 May;83(9):4605-15.

 
6. Adaptation of HIV-1 to human leukocyte antigen class I. Nature. 2009 Apr 2;458(7238):641-5. Epub 2009 Feb 25.

 
7. Compensatory mutation partially restores fitness and delays reversion of escape mutation within the immunodominant HLA-B*5703-restricted Gag epitope in chronic human immunodeficiency virus type 1 infection. J Virol. 2007 Aug;81(15):8346-51.

 
Learn More