Host-cell sensors for Plasmodium activate innate immunity against liver-stage infection

Nature Medicine Cover (Jan 2014)

During the break, another paper where I played a part came out and now is it on the cover of the January edition of Nature Medicine:

Host-cell sensors for Plasmodium activate innate immunity against liver-stage infection by Liehl et al., in Nature Medicine 20, 47-53  (2014) [DOI]

Plasmodium, the malaria causing parasite, when entering the human body, first infects the liver. There, the small number of initial parasites (perhaps only a handful of them), multiply until they burst into the blood stream where they cause havoc, which can have potentially fatal consequences if left untreated.

The liver stage is clinically silent, with no visible symptoms. However, it does not go completely undetected by the host’s immune system. There were previous reports of an immune response in the liver, but we worked on understanding more of what was going on and observed a type-I interferon response using transcriptomics.

What I thought was most surprising (although this may be a function of my naïveté) was that the response seems to be activated by RNA sensing. The host detects the Plasmodium RNA and that triggers an immune response. This is some bad ass immune system stuff: using RNA sensors against eukariotic parasites instead of just viruses.


Nature Medicine thought this was cool too and wrote up summary as well as putting the paper on the cover of January edition!

This excellent work must be credited to Peter Liehl and Maria Mota (the first and last authors). I am just happy that I got to play a role in this enterprise and learn some cool biology.


Notes on #ISMBECCB Highlights Session (Sunday Morning)

(I missed the first half of the first talk, so I won’t include it. Also, the internet is not good enough for me to get all the links. Sorry)

Of Men and Not Mice: Comparative Genomic Analysis of Human Diseases and Mouse Models by Wenzhong Xiao

Wenzhong Xiao presented an empirical study of correlation between immune response of mice and men. The correlations were very low, which is a warning to be careful in interpreting animal models results. Money quote: “Mice are not human. There are several reasons for that.”

An audience member raised the possibility of using humanized models, which was a great point. I’ll add that the immune system and immune system dysfunction may be where mice and men differ the most and results there do not invalidate results in other areas of study.

Impact of genetic dynamics and single-cell heterogeneity on development of nonstandard personalized medicine strategies for cancer by Chen-Hsiang Yeang

Simulation study of using different strategies for cancer treatment in the present of resistant mutations. “The current system is often like a greedy algorithm: do X until resistance to X emerges, switch to Y. Repeat. Better strategies are possible.”

Very interesting points come out of simple models, but it felt like the start of a conversation rather than an answer.

Interesting presentation detail: author used references to video games as one would use references to literature 100 years ago.

Systems-based metatranscriptomic analysis by Xuejian Xiong.

Original Paper: He, D., Miao, M., Sitarz, E.E., Muiznieks, L.D., Reichheld, S., Stahl, R.J., Keeley, F.W. and Parkinson, J. (2012) Polymorphisms in the Human Tropoelastin Gene Modify in vitro Self-Assembly and Mechanical Properties of Elastin-like Polypeptides. PLoS ONE. 7(9): e46130

Study on non-obese diabetic mice with Illumina sequencing. They projected their reads into enzyme space to perform analysis at the metabolic network level.

Interesting technical points: they use alignment in peptide space instead of nucleotide space to get around variability in codon encoding. They also found that Trinity worked best for their data.