Biophysical Society Thematic Meeting - November 16-20, 2015

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Biophysics in the Understanding, Diagnosis, and Treatment of Infectious Diseases Poster Abstracts
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24-POS Board 24
LncRNA Discovery in Host-Pathogen Interactions
Loretta Magagula1,2,3, Janine Scholefield1,2, Youtaro Shibayama1,2, Joana Cruz4, Frank
Brombacher3 , Musa Mhlanga2,3,4.
1Council of Scientific & Industrial Research (CSIR), Pretoria, Gauteng, South
Africa, 2 University of Cape Town, Cape Town, Western Cape, South Africa, 4Universidade de
Lisboa, Lisboa, Portugal.3University of Cape Town, Cape Town, Western Cape, South Africa,
In the last year alone, a handful of studies have identified long noncoding RNAs (lncRNAs) linc-
Cox2, Lethe, PACER and THRIL as central molecular players in host cell innate immune
response against microbial infection. Gene regulation has emerged as a prevailing theme in
lncRNA functioning. These discoveries and the vast numbers of uncharacterized lncRNAs
identified by high-throughput next-generation transcriptome sequencing technologies, set a
precedence for further investigation and characterization of lncRNAs in infection biology.
Importantly, lncRNAs may serve as important diagnostic markers of infection as well as
therapeutic targets. These aspects, although extensively being explored in cancer research, have
been neglected in infection biology, particularly in microbial infection.
In this study, RNA-Sequencing (RNA-Seq) was used to identify subtle vairations in
transcriptional activity, with particular emphasis on lncRNA differential expression, and uncover
their physiological relevance during Listeria monotocytogenes infection. To this end, an RNA-
Seq dataset of Listeria-infected HeLa cells was subjected to several variations of data analysis
lncRNA discovery pipelines. Potential lncRNA functioning was hypothesized using a derivation
of the Rinn & Chang “guilt by association” approach in which lncRNA functioning was
hypothesized based on known functions of tightly co-expressed protein coding mRNAs. “Guilty”
lncRNAs were then knocked down in the HeLa cells using transcription activator-like nucleases
(TALENs) to validate their candidacy as infection-regulating lncRNAs. Preliminary
investigations conducted in this study have revealed potential Listeria infection-inhibiting
lncRNA candidates in the HeLa cell model. Furthermore, we are currently exploring the use of a
physiologically relevant cellular model, induced pluripotent stem cell (iPSC) monocyte derived
macrophages (MDMs), to validate identified lncRNA candidates.