Inhibitors of mitochondrial gene transcription

Research

The laboratory investigates the mechanisms of mammalian mitochondrial transcription. The levels of mitochondrial transcription are regulated in response to the overall respiratory needs of the eukaryotic cell, but the molecular mechanisms behind this regulation are poorly understood. Much of the work is performed using in vitro biochemistry and a reconstituted system for mammalian mtDNA transcription, containing only a promoter containing DNA fragment, and recombinant proteins. One of our areas of interest is the MTERF family of proteins. These proteins regulate mitochondrial gene expression at many different levels, including transcription initiation, transcription termination, and during protein translation. We are also studying DNA sequence dependent transcription termination in mitochondria. In our work, we have seen that a G-quadruplex structure formed in nascent RNA during transcription can stimulate termination. The mechanism is reminiscent of Rho-independent transcription termination in prokaryotes, with the exception that a G-quadruplex structure replaces the hairpin loop formed in bacterial mRNA during transcription of terminator sequences.

Latest Publications

Shi Y, Posse V, Zhu X, Hyvärinen AK, Jacobs HT, Falkenberg M, Gustafsson CM. (2016) Mitochondrial transcription termination factor 1 directs polar replication fork pausing. Nucleic Acids Res. 44(12):5732-42. doi: 10.1093/nar/gkw302. Epub 2016 Apr 25.

Stewart JB, Alaei-Mahabadi B, Sabarinathan R, Samuelsson T, Gorodkin J, Gustafsson CM, Larsson E. (2015) Simultaneous DNA and RNA Mapping of Somatic Mitochondrial Mutations across Diverse Human Cancers. PLoS Genet. 11(6):e1005333. doi: 10.1371/journal.pgen.1005333. eCollection 2015 Jun.

Posse V, Shahzad S, Falkenberg M, Hällberg BM, Gustafsson CM. (2015) TEFM is a potent stimulator of mitochondrial transcription elongation in vitro. Nucleic Acids Res. 43(5):2615-24. doi: 10.1093/nar/gkv105. Epub 2015 Feb 17.

PhD position filled!

The PhD position has been filled. Thank you for your interest!

Information

We are looking for a highly qualified and motivated researcher to join our team to investigate the mitochondrial RNA polymerase and its mechanism of action. In the laboratory, we employ in vitro biochemistry and cell biology techniques to study mitochondrial transcription. We also use cell-biological techniques to identify and characterize new proteins involved in these processes.

Project title: The mitochondrial RNA polymerase and its regulation

Job assignments: In the PhD project, we will investigate the structure and function of the single subunit RNA polymerase, POLRMT, present in human mitochondria. The project includes work to characterize how mitochondrial transcription is regulated in response to the metabolic needs of the mammalian cell.

The ideal candidate should have an interest in biochemistry and molecular biology and moreover cloning, mutagenesis, protein expression and purification. The work involves collaboration within and outside the group, therefore good teamwork skills are important. The project requires an enthusiastic and creative person with a passion and curiosity for science. Good English is required since we operate in a very international environment. 

The PhD position comprises 4 years full-time studies and leads to a doctoral degree.

How to apply: For detailed information about the project, eligibility, and how to apply, interested candidates should contact the principal scientist, Claes Gustafsson (claes.gustafsson@medkem.gu.se). The deadline for applications is set to December 2, 2016.