News in our group
Welcome to our new Master's student starting from 2022
Great welcome to Bjørn Christian Lundberg, Sharika Marjan, and Tsering Yangzom to join our MMN group and work on different stem cell projects. We wish you a great achievement during your masters' study.
NEWS ON STEM CELL STUDY
Our group has just published a major study in Frontiers in Cell and Developmental Biology. In this study, we reveal that impaired mitophagy is involved in the observed mitochondrial dysfunction caused by POLG mutations in astrocytes, potentially contributing to the phenotype in POLG-related diseases. This study also demonstrates the therapeutic potential of NR and metformin in these incurable mitochondrial diseases.
NEW DISSERTATION IN DECEMBER 2021
Kristin Nielsen Varhaug will present her dissertation for the Ph.D. degree with the thesis "Mitochondrial biomarkers and biomarkers of mitochondrial disease" on November 26th, 2021. The main supervisor for this thesis was Professor Laurence A. Bindoff and co-supervisor was Professor Christian A. Vedeler.
In this study, we established for the first time a direct link between an altered mitochondrial function and amyloid neurodegeneration.
In this collaborative study, we described the first family with a (recessive) pathological mutation in the gene encoding PITRM1, the mitochondrial matrix metallopeptidase that digests mitochondrial targeting sequences after cleavage by the mitochondrial matrix peptidase. The PITRM1 mutation was associated with a slowly progressive neurodegenerative condition characterized by mild mental retardation, spinocerebellar ataxia with cerebellar atrophy, and psychosis.
We confirmed the pathogenicity of the mutation by investigating mutant and RNAi cells, and a yeast model (the yeast ortholog is CYM1). In vitro assays carried out on the recombinant protein expressed in E. coli, led us to conclude that the mutation causes severe protein instability mimicking a condition of haploinsufficiency. Investigations of a Pitrm1-/+ mouse model (the Pitrm1-/- individuals are embryonic lethal), also showed reduced Pitrm1 protein in different tissues and the animals developed a progressive neurological syndrome characterized by ataxia, behavioral impairment, and abnormal bioenergetics parameters in vivo.
Interestingly, neuropathological investigation of these animals revealed the accumulation of Amyloid Precursor Protein and amyloid-beta (Aβ) deposits, similar to the amyloid plaques seen in Alzheimer's disease brains (see figure). The accumulation of Aβ supports the hypothesis that PITRM1 is involved in the quantitative digestion of a fraction of Aβ and that this protein product is indeed contained within mitochondria. This observation has been controversial and our findings confirm this for the first time in a mammalian model.
This work was a collaboration between groups from Norway (Bergen - MMN & Center for Medical Genetics and Molecular Medicine; Førde), UK (MBU, Cambridge), Italy (Rome, Parma) and Sweden (Stockholm)
Omar Hikmat presented his dissertation for the Ph.D. degree with the thesis "The phenotypic spectrum of polymerase gamma (POLG) disease from birth to late adulthood" on September 25th, 2020. The main supervisor for this thesis was Professor Laurence A. Bindoff and the co-supervisor was Professor Charalampos Tzoulis.
Using stem cell technology, our group has managed to reconstruct disease progression in mitochondrial failure. This can be a step towards the treatment of severe epilepsy and other brain diseases. Our group has managed to reconstruct disease progression in mitochondrial failure. This can be a step towards the treatment of severe epilepsy and other brain diseases. The study is published in EMBO Molecular Medicine.
Our group has attended the 6th Bergen Stem cell Consortium (BSCC) annual meeting in Solstrand Hotel & Bad on 19-20, October 2019. , This is a networking event with basic and clinical research updates in the field of stem cells and regenerative medicine. Senior researcher Kristina Xiao Liang presented a talk on “Using induced pluripotent stem cells (iPSCs) to model mitochondrial disease, study tissue-specific manifestations and investigate treatments”. Postdoc. Yu Hong and Ph.D. fellows Cecilie, Sepideh, and Anbin gave a lightning talk in the meeting.
Our group has recently published a new paper on “A method for differentiating human induced pluripotent stem cells toward functional cardiomyocytes in 96-well microplates”. In this study, Novin Balafkan (first author) and Sepideh Mostafavi (co-first author) et al. developed a protocol for efficient differentiation towards cardiomyocytes from iPSCs using a defined, serum-free culture medium combined with small molecules. We believe that this technique will improve the applicability of these cells for use in developmental biology and mechanistic studies of disease. The study is published in Scientific Report.
5th BSCC ANNUAL MEETING
As one of the research groups in Bergen Stem Cell Consortium (BSCC). We have organized and attended the 5th BSCC annual meeting in Hotel Scandic Ørnen on 3-4, October 2019.