Berridge Laboratory

The Berridge Laboratory focuses on understanding cell metabolism in relation to cancer and neurodegenerative diseases.

Cancer cells are known to alter their metabolism, changing the balance between mitochondrial and glycolytic production of ATP to allow them to better survive and metastasise. Previous work in the Berridge Laboratory revealed that cells entirely lacking mitochondrial DNA were unable to respire and form tumours unless they acquired mitochondria with mitochondrial DNA from normal cells via mitochondrial transfer.

The group is also following on from work that previously showed an up-regulation in chemokine signalling and other immune-related genes in cells under this metabolic stress. The team is investigating the modulation between mitochondrial and glycolytic ATP generation with altered mtDNA, what cell signals are the drivers of mitochondrial transfer, what immune responses are involved, and whether mitochondrial ATP is required for metastasis.

This research will help identify potential gene targets for preventing cancer cells from modifying their metabolism, carrying out mitochondrial transfer, and blocking immune interference in metastasis.

The Berridge Laboratory is also working on developing a gene expression based assay for Parkinson’s disease. This project involves monitoring the expression of a small number of genes that represent each complex of the electron transport chain coded for in the mitochondrial DNA, complex I, III, IV and V. This will be used to determine whether early changes in olfactory cells have the predictive power to diagnose Parkinson’s disease before onset of symptoms, and has the potential to become an applied diagnostic technique.

Research areas

• Bioenergetic control of cancer metastasis
• Neurodegenerative diseases: early detection
• Intranasal vaccines for respiratory viruses

Research projects

• The role of respiration and ATP production in tumorigenesis and metastasis
• Early mitochondrial dysfunction assay for neurodegenerative diseases
• Towards effective mucosal vaccines against respiratory virus infections

Collaborations

• School of Pharmacy and Medical Sciences, Griffith University
• Institute of Biotechnology (BIOCEV), Czech Republic
• Victoria University of Wellington - Te Herenga Waka
• Jenner Institute, University of Oxford

Tan AS, Baty JW, Dong LF, Bezawork-Geleta A, Endaya B, Goodwin J, Bajzikova M, Kovarova J, Peterka M, Yan B, Pesdar EA, Sobo M, Filimonenko A, Stuart S, Vondrusova M, Kluckova K, Sachaphibulkij K, Rohlena J, Hozak P, Truksa J, Eccles D, Haupt LM, Griffiths LR, Neuzil J, Berridge MV (2015) Mitochondrial Genome Acquisition Restores Respiratory Function and Tumorigenic Potential of Cancer Cells without Mitochondrial DNA. Cell Metab

Berridge MV, Dong L, Neuzil J (2015) Mitochondrial DNA in tumor initiation, progression and metastasis: role of horizontal mtDNA transfer. Cancer Res

Berridge MV, Schneider R, McConnell MJ (2016) Mitochondrial transfer from astrocytes to neurons following ischemic insult: guilt by association? Cell Metab

Berridge MV, McConnell MJ, Grasso C, Bajzikova M, Kovarova J, Neuzil J (2016) Horizontal transfer of mitochondria between mammalian cells: beyond co-culture approaches. Curr Opin Genetics Dev

Dong L-F, Kovarova J, Bajzikova M, Bezawork-Geleta A, Svec D, Endaya B, Sachaphibulkij K, Coelho AR, Sebkova N, Ruzickova A, Tan AS, Kluckova K, Judasova K, Zamecnikova K, Rychtarcikova Z, Gopalan V, Andera L, Sobol M, Yan B, Pattnaik B, Bhatraju N, Truksa J, Stopka P, Hozak P, Lam A, Sedlacek, R, Oliveira P, Kubista M, Agrawal A, Dvorakova-Hortova K, Rohlena J, Berridge MV, Neuzil J (2017) Horizontal transfer of whole mitochondria restores tumorigenic potential in mitochondrial DNA-deficient cancer cells. eLife

Herst PM, Rowe MR, Carson GM, Berridge MV. (2017) Functional Mitochondria in Health and Disease. Front Endocrinol (Lausanne)

Berridge MV, Herst PM, Rowe MR, Schneider R, McConnell MJ. (2018). Mitochondrial transfer between cells: Methodological constraints in cell culture and animal models. Anal Biochem.

Bezawork-Geleta A, Wen H, Dong L, Yan B, Vider J, Boukalova S, Krobova L, Vanova K, Zobalova R, Sobol M, Hozak P, Novais SM, Caisova V, Abaffy P, Naraine R, Pang Y, Zaw T, Zhang P, Sindelka R, Kubista M, Zuryn S, Molloy MP, Berridge MV, Pacak K, Rohlena J, Park S, Neuzil J. (2018). Alternative assembly of respiratory complex II connects energy stress to metabolic checkpoints. Nat Commun

Herst PM, Dawson, RH, Berridge MV (2018) Intercellular communication in Tumour Biology: A Role for Mitochondrial Transfer. Frontiers in Oncol 8:344

Bajzikova M, Kovarova J, Coelho AR, Boukalova S, Oh S, Rohlenova K, Svec D, Hubackova S, Endaya B, Judasova K, Bezawork-Geleta A, Kluckova K, Chatre L, Zobalova R, Novakova A, Vanova K, Ezrova Z, Maghzal GJ, Magalhaes Novais S, Olsinova M, Krobova L, An YJ, Davidova E, Nahacka Z, Sobol M, Cunha-Oliveira T, Sandoval-Acuña C, Strnad H, Zhang T, Huynh T, Serafim TL, Hozak P, Sardao VA, Koopman WJH, Ricchetti M, Oliveira PJ, Kolar F, Kubista M, Truksa J, Dvorakova-Hortova K, Pacak K, Gurlich R, Stocker R, Zhou Y, Berridge MV, Park S, Dong L, Rohlena J, Neuzil J (2019) Reactivation of Dihydroorotate Dehydrogenase-Driven Pyrimidine Biosynthesis Restores Tumor Growth of Respiration-Deficient Cancer Cells. Cell Metab 29(2):399-416.e10

Grasso C, Eccles DA, Boukalova S, Fabre M-S, Dawson RH, Neuzil J, Herst PM, Berridge MV. (2020) Mitochondrial DNA affects expression of nuclear genes involved in immune and stress responses in a breast cancer model. Frontiers in Physiology: Mitochondrial Research. 11: 543962. doi: 10.3389/fphys.2020.543962,