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School of Biological and Behavioural Sciences

Dr Charalampos (Babis) Rallis

Charalampos (Babis)

Reader in Genetics, Genomics and Fundamental Cell Biology, Director of Industrial Innovation, Theme Leader for Genetics of Disease and Ageing

Email: c.rallis@qmul.ac.uk
Room Number: 4.14, Fogg Building
Website: https://www.rallislab.org/
Twitter: @rallislab

Profile

Following his PhD studies on limb development with Prof Malcolm Logan at the MRC National Institute for Medical Research, Babis did postdoctoral research on single cell expression profiling of axial stem cells and integrin signalling during somitogenesis with Prof David Ish-Horowicz FRS at the CRUK Lincoln's Inn Fields Laboratories. This was followed by a Research Associate position with Prof Jurg Bahler at the UCL Institute of Healthy Ageing working on nutrient-responsive pathways, ageing mechanisms, quiescence and senescence. 

Babis moved to the University of Essex in 2020 where he established his own independent research group.  He joined the School of Biological and Behavioural Sciences in September 2023. 

The Rallislab investigates gene and protein networks implicated in cellular fitness and metabolism, neurodegeneration, cancer and ageing with a focus on the nutrient-responsive signalling pathway mechanistic Target of Rapamycin (mTOR). The aim of the group is to elucidate the molecular mechanisms and principles behind senescence and lifespan and apply this knowledge for the amelioration, or even prevention, of age-related diseases. In addition, the group performs quantitative fitness profiling of microbial strains, microbiomes and mycobiomes and explore the effects of nutrition on biome physiology and subsequent effects on human healthy ageing. The group uses established and relevant cellular systems such as the fission yeast Schizosaccharomyces pombe and mammalian 2D and 3D tissue culture systems such as fibroblasts, cancer cell lines, human dopaminergic and iPSC-derived motor neurons. Besides classical molecular biology, genetic, cell biology and microscopy approaches, the group utilises multi-omics (transcriptome, proteome, metabolome and phenome approaches) as well as related data integrations and network biology. 

Teaching

Essential Skills for Biomedical Scientists (BMD100)

Structured Research Project (BIO604)

Research

Research Interests:

Transcriptional networks in ageing and neurodegeneration

Using 2D/3D human neuronal cultures as well as genetic approaches in the fruitfly Drosophila melanogaster we analyze gene and protein networks in normal and pathological conditions during TOR-active and inactive states. We use transcriptomics and proteomics and data integrations towards elucidating the role of TOR in neurodegeneration and identifying molecular markers, players and targets for interventions. Through this program we have identified novel cases of transcription factors that mediate mTOR-related processes and cellular metabolism. We analyse their targets and how to finely tune their activities.

Integrating cellular space and time in physiology, disease and ageing

The connections between nutrient availability, TOR and length of life have been studied intensively. These studies have shown that TOR controls the amount as well as the quality of the proteins produced within cells together with the recycling of biological material (a process that is known as 'autophagy'). High amounts of protein production and reduction in the recycling quality are detrimental. We and others have found such physical and genetic connections and have provided additional potential targets for drug development against age-related diseases. However, the connections and workings between cellular space and lifespan are not well understood. Using fission yeast and mammalian tissue culture systems we investigate these interplays towards providing a knowledge platform for promoting healthy ageing.

Mechanisms of uncoupling cellular growth from nutrient availability and mTOR pathway activity

Inhibition of TOR through genetic or pharmacological means has a profound negative effect on cell growth. Mutated and overactivated TOR pathway is directly implicated in many cancers and numerous clinical trials are currently ongoing. However, cells (including cancer cells) are able to rewire their metabolism and resume growth in states where TOR is inhibited. This phenomenon shows that there are mechanisms of bypassing the requirements of TOR for growth and, essentially, uncouple nutrient and growth factor availability from cell division. Nevertheless, these mechanisms are not well understood. By utilising multi-omics and network biology we start revealing a comprehensive genetic connectivity roadmap of the molecular mechanisms involved in this TOR-resistance phenomena. Our results will directly point towards possible vulnerabilities of resistant cells that can be further exploited in cancer biology and beyond. 

Examples of research funding:

The Rallis Lab is funded through:

-UKRI Medical Research Council

-UKRI Biotechnology and Biological Sciences Research Council

-The Royal Society

-Queen Mary University of London

Publications

Islam RA and Rallis C. (2023). Ribosomal Biogenesis and Heterogeneity in Development, Disease, and Aging. Epigenomes. 2023 Aug 11;7(3):17. doi: https://doi.org/10.3390/epigenomes7030017

Alao JP and Rallis C. (2023). The AMPK-TORC1 signalling axis regulates caffeine-mediated DNA damage checkpoint override and cell cycle effects in fission yeast. bioRxiv 2022.11.08.515652; doi: https://doi.org/10.1101/2022.11.08.515652.

Alao JP, Legon L, Dabrowska A, Tricolici AM, Kumar J, Rallis C. (2023). Interplays of AMPK and TOR in Autophagy Regulation in Yeast. Cells. 2023 Feb 4;12(4):519. doi: 10.3390/cells12040519.

Dabrowska A, Kumar J, Rallis C. (2022). Nutrient-Response Pathways in Healthspan and Lifespan Regulation. Cells. 2022 May 6;11(9):1568. doi: 10.3390/cells11091568. 

Martinez-Miguel V.E., Lujan C., Espie--Caullet T., Martinez-Martinez D., Moore S., Backes C., Gonzalez S., Galimov E., Brown A.E.X., Halic M., Tomita K., Rallis C., von der Haar T., Cabreiro F., and Bjedov, I., (2021). Increased fidelity of protein synthesis extends lifespan. Published:September 14, 2021DOI: https://doi.org/10.1016/j.cmet.2021.08.017.

Alao, J-P., Legon, L. and Rallis, C., (2021). Crosstalk between the mTOR and DNA Damage Response Pathways in Fission Yeast. Cells. 10 (2), 305-305

Legon, L. and Rallis, C., (2021). Genome-wide screens in yeast models towards understanding chronological lifespan regulation. Briefings in Functional Genomics

Rallis, C., Mülleder, M., Smith, G., Au, YZ., Ralser, M. and Bähler, J., (2021). Amino acids whose intracellular levels change most during aging alter chronological lifespan of fission yeast. Journals of Gerontology - Series A. 76 (2), 205-210

Rodríguez-López, M., Gonzalez, S., Hillson, O., Tunnacliffe, E., Codlin, S., Tallada, VA., Bähler, J. and Rallis, C., (2020). The GATA Transcription Factor Gaf1 Represses tRNAs, Inhibits Growth, and Extends Chronological Lifespan Downstream of Fission Yeast TORC1. Cell Reports. 30 (10), 3240-3249.e4

Bjedov, I. and Rallis, C., (2020). The Target of Rapamycin Signalling Pathway in Ageing and Lifespan Regulation. Genes. 11 (9), 1043-1043

Alao, JP., Johansson-Sjölander, J., Rallis, C. and Sunnerhagen, P., (2020). Caffeine Stabilises Fission Yeast Wee1 in a Rad24-Dependent Manner but Attenuates Its Expression in Response to DNA Damage. Microorganisms. 8 (10), 1512-1512

Pai, C-C., Hsu, K-F., Durley, SC., Keszthelyi, A., Kearsey, SE., Rallis, C., Folkes, LK., Deegan, R., Wilkins, SE., Pfister, SX., De León, N., Schofield, CJ., Bähler, J., Carr, AM. and Humphrey, TC., (2019). An essential role for dNTP homeostasis following CDK-induced replication stress. Journal of Cell Science. 132 (6)

Hillson, O., Gonzalez, S. and Rallis, C., (2018). Prospects of Pharmacological Interventions to Organismal Aging. BioMolecular Concepts. 9 (1), 200-215

Ellis, DA., Mustonen, V., Rodríguez-López, M., Rallis, C., Malecki, M., Jeffares, DC. and Bähler, J., (2018). Uncovering Natural Longevity Alleles from Intercrossed Pools of Aging Fission Yeast Cells. Genetics. 210 (2), 733-744

Atkinson, SR., Marguerat, S., Bitton, DA., Rodríguez-López, M., Rallis, C., Lemay, J-F., Cotobal, C., Malecki, M., Smialowski, P., Mata, J., Korber, P., Bachand, F. and Bähler, J., (2018). Long noncoding RNA repertoire and targeting by nuclear exosome, cytoplasmic exonuclease, and RNAi in fission yeast. RNA. 24 (9), 1195-1213

Hoyos-Manchado, R., Reyes-Martín, F., Rallis, C., Gamero-Estévez, E., Rodríguez-Gómez, P., Quintero-Blanco, J., Bähler, J., Jiménez, J. and Tallada, VA., (2017). RNA metabolism is the primary target of formamide in vivo. Scientific Reports. 7 (1), 15895-

Gonzalez, S. and Rallis, C., (2017). The TOR Signaling Pathway in Spatial and Temporal Control of Cell Size and Growth. Frontiers in Cell and Developmental Biology. 5 (JUN)

Rallis, C., Townsend, S. and Bähler, J., (2017). Genetic interactions and functional analyses of the fission yeast gsk3 and amk2 single and double mutants defective in TORC1-dependent processes. Scientific Reports. 7 (1), 44257-

Jeffares, DC., Jolly, C., Hoti, M., Speed, D., Shaw, L., Rallis, C., Balloux, F., Dessimoz, C., Bähler, J. and Sedlazeck, FJ., (2017). Transient structural variations have strong effects on quantitative traits and reproductive isolation in fission yeast. Nature Communications. 8 (1), 14061-

Malecki, M., Bitton, DA., Rodríguez-López, M., Rallis, C., Calavia, NG., Smith, GC. and Bähler, J., (2016). Functional and regulatory profiling of energy metabolism in fission yeast. Genome Biology. 17 (1), 240-

Brault, A., Rallis, C., Normant, V., Garant, J-M., Bähler, J. and Labbé, S., (2016). Php4 Is a Key Player for Iron Economy in Meiotic and Sporulating Cells. G3: Genes, Genomes, Genetics. 6 (10), 3077-3095

Rallis, C. and Bähler, J., (2016). Cell-based screens and phenomics with fission yeast.. Critical Reviews in Biochemistry and Molecular Biology. 51 (2), 86-95

Tomalin, LE., Day, AM., Underwood, ZE., Smith, GR., Dalle Pezze, P., Rallis, C., Patel, W., Dickinson, BC., Bähler, J., Brewer, TF., Chang, CJ-L., Shanley, DP. and Veal, EA., (2016). Increasing extracellular H₂O₂ produces a bi-phasic response in intracellular H₂O₂, with peroxiredoxin hyperoxidation only triggered once the cellular H₂O₂-buffering capacity is overwhelmed. Free Radical Biology and Medicine. 95, 333-348

Vishwanatha, A., Rallis, C., Bevkal Subramanyaswamy, S., D'Souza, CJM., Bähler, J. and Schweingruber, ME., (2016). Identification of nuclear genes affecting 2-Deoxyglucose resistance in Schizosaccharomyces pombe.. FEMS Yeast Research. 16 (6), fow061-fow061

Bischof, L., Převorovský, M., Rallis, C., Jeffares, DC., Arzhaeva, Y. and Bähler, J., (2016). Spotsizer: High-throughput quantitative analysis of microbial growth.. BioTechniques. 61 (4), 191-201

Bond, M., Brown, R., Rallis, C., Bahler, J. and Mole, S., (2015). A central role for TOR signalling in a yeast model for juvenile CLN3 disease. Microbial Cell. 2 (12), 466-480

Jeffares, DC., Rallis, C., Rieux, A., Speed, D., Převorovský, M., Mourier, T., Marsellach, FX., Iqbal, Z., Lau, W., Cheng, TMK., Pracana, R., Mülleder, M., Lawson, JLD., Chessel, A., Bala, S., Hellenthal, G., O'Fallon, B., Keane, T., Simpson, JT., Bischof, L., Tomiczek, B., Bitton, DA., Sideri, T., Codlin, S., Hellberg, JEEU., van Trigt, L., Jeffery, L., Li, J-J., Atkinson, S., Thodberg, M., Febrer, M., McLay, K., Drou, N., Brown, W., Hayles, J., Carazo Salas, RE., Ralser, M., Maniatis, N., Balding, DJ., Balloux, F., Durbin, R. and Bähler, J., (2015). The genomic and phenotypic diversity of Schizosaccharomyces pombe.. Nature Genetics. 47 (3), 235-241

Bitton, DA., Atkinson, SR., Rallis, C., Smith, GC., Ellis, DA., Chen, YYC., Malecki, M., Codlin, S., Lemay, J-F., Cotobal, C., Bachand, F., Marguerat, S., Mata, J. and Bähler, J., (2015). Widespread exon skipping triggers degradation by nuclear RNA surveillance in fission yeast.. Genome Research. 25 (6), 884-896

Sideri, T., Rallis, C., Bitton, DA., Lages, BM., Suo, F., Rodríguez-López, M., Du, L-L. and Bähler, J., (2015). Parallel profiling of fission yeast deletion mutants for proliferation and for lifespan during long-term quiescence.. G3: Genes, Genomes, Genetics. 5 (1), 145-155

Bitton, DA., Rallis, C., Jeffares, DC., Smith, GC., Chen, YYC., Codlin, S., Marguerat, S. and Bähler, J., (2014). LaSSO, a strategy for genome-wide mapping of intronic lariats and branch points using RNA-seq.. Genome Research. 24 (7), 1169-1179

Sofola-Adesakin, O., Castillo-Quan, JI., Rallis, C., Tain, LS., Bjedov, I., Rogers, I., Li, L., Martinez, P., Khericha, M., Cabecinha, M., Bähler, J. and Partridge, L., (2014). Lithium suppresses Aβ pathology by inhibiting translation in an adult Drosophila model of Alzheimer's disease.. Frontiers in Aging Neuroscience. 6 (JUL)

Rallis, C., López-Maury, L., Georgescu, T., Pancaldi, V. and Bähler, J., (2014). Systematic screen for mutants resistant to TORC1 inhibition in fission yeast reveals genes involved in cellular ageing and growth.. Biology Open. 3 (2), 161-171

Rallis, C. and Bähler, J., (2013). Inhibition of TORC1 signaling and increased lifespan: gained in translation?. Aging. 5 (5), 335-336

Rallis, C., Codlin, S. and Bähler, J., (2013). TORC1 signaling inhibition by rapamycin and caffeine affect lifespan, global gene expression, and cell proliferation of fission yeast.. Aging Cell. 12 (4), 563-573

Pancaldi, V., Saraç, OS., Rallis, C., McLean, JR., Převorovský, M., Gould, K., Beyer, A. and Bähler, J., (2012). Predicting the fission yeast protein interaction network.. G3: Genes, Genomes, Genetics. 2 (4), 453-467

Převorovský, M. and Rallis, C., (2011). Bright days for yeast research. Genome Biology. 12 (5), 305-305

Rallis, C., Pinchin, SM. and Ish-Horowicz, D., (2010). Cell-autonomous integrin control of Wnt and Notch signalling during somitogenesis. Development. 137 (21), 3591-3601

Maydan, M., McDonald, PC., Sanghera, J., Yan, J., Rallis, C., Pinchin, S., Hannigan, GE., Foster, LJ., Ish-Horowicz, D., Walsh, MP. and Dedhar, S., (2010). Integrin-linked kinase is a functional Mn²⁺-dependent protein kinase that regulates glycogen synthase kinase-3β (GSK-3beta) phosphorylation.. PLoS One. 5 (8), e12356-e12356

Rallis, C., (2009). New tricks for an old-favorite model. Genome Biology. 10 (9), 315-315

Hanisch, A., Vezzaro, A. and Rallis, C., (2008). Elucidating developmental gene networks. Genome Biology. 9 (6), 310-310

Bazigou, E. and Rallis, C., (2007). Cell signaling and cancer. Genome Biology. 8 (7), 310-310

Rallis, C., (2007). Chickens get their place in the sun. Genome Biology. 8 (5), 306-306

Rallis, C., (2006). Developmental genomics reaches new heights.. Genome Biology. 7 (10), 329-329

Rallis, C., Del Buono, J. and Logan, MPO., (2005). Tbx3 can alter limb position along the rostrocaudal axis of the developing embryo.. Development. 132 (8), 1961-1970

Rallis, C., Bruneau, BG., Del Buono, J., Seidman, CE., Seidman, JG., Nissim, S., Tabin, CJ. and Logan, MPO., (2003). Tbx5 is required for forelimb bud formation and continued outgrowth. Development. 130 (12), 2741-2751

Rallis, CP. and Burand, JP., (2002). Pathology and ultrastructure of Hz-2V infection in the agonadal female corn earworm, Helicoverpa zea. Journal of Invertebrate Pathology. 81 (1), 33-44

Rallis, C., Stamataki, D., Pontikakis, S., Mankoo, BS. and Karagogeos, D., (2001). Isolation of the avian homologue of the homeobox gene Mox2 and analysis of its expression pattern in developing somites and limbs.. Mechanisms of Development. 104 (1-2), 121-124

Supervision

Olga Xintarakou-PhD student

Luc Legon-PhD student

Riaz Ali-Somji-PhD student

Anne-Marie Tricolici-MRes/MSD student

Dr John-Patrick Alao-postdoc

Dr Juhi Kumar-postdoc

Dr Rowshan Islam-postdoc

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