22.1. 2019, Bioenergetika

PhD project: Impact of mitochondrial DNA diversity on metabolic phenotype and innate immunity

Recently, metabolic syndrome has been associated with chronic, low-grade systemic inflammation, increased immunogenetic susceptibility and rise in circulating immune markers. Interestingly, incidence of some of the hallmarks of metabolic syndrome (e.g. type 2 diabetes) differs among ethnicities - while part of the variability may be explained by different quality of care between ethnic groups, others seem to stem from genetic diversity. An important role may be played by physiological genetic diversity of maternally inherited mitochondrial DNA. Remarkably, mitochondria have also been demonstrated to trigger host immune response, namely by activating innate immune system.

In the current project we will utilize the model of rat conplastic strains with several mtDNA haplogroups present on identical nuclear background. We will test the hypothesis that the naturally occurring mtDNA diversity influences systemic inflammation status and further explore pathways involved in this process. Subsequently, the propensity towards development of metabolic syndrome and innate immunity response during metabolic challenge will be tested.

Candidate’s profile (requirements):

We are seeking for highly-motivated person with MSc. or equivalent degree in cell biology, biochemistry, immunology, physiology or similar field obtained before or during 2019. Candidate should be fluent in English and apart from the experimental “wet” work, she/he should be willing to work with laboratory animals.

Relevant publications:

Pecinova A, Drahota Z, Kovalcikova J, Kovarova N, Pecina P, Alan L, Zima M, Houstek J, Mracek T. Pleiotropic Effects of Biguanides on Mitochondrial Reactive Oxygen Species Production. Oxid Med Cell Longev. 2017;2017:7038603

Shabalina IG, Vrbacky M, Pecinova A, Kalinovich AV, Drahota Z, Houstek J, Mracek T, Cannon B, Nedergaard J. ROS production in brown adipose tissue mitochondria: the question of UCP1-dependence. Biochim Biophys Acta. 2014 Dec;1837(12):2017-2030

Houstek J, Hejzlarova K, Vrbacky M, Drahota Z, Landa V, Zidek V, Mlejnek P, Simakova M, Silhavy J, Miksik I, Kazdova L, Oliyarnyk O, Kurtz T, Pravenec M. Nonsynonymous variants in mt-Nd2, mt-Nd4, and mt-Nd5 are linked to effects on oxidative phosphorylation and insulin sensitivity in rat conplastic strains. Physiol Genomics. 2012 May 1;44(9):487-94

Supervisor: RNDr. Alena Pecinová, Ph.D.