Force generation principles in dividing cells
Molecular and Cell Biology, Biochemistry and Quantitative AnalysisExplore
Regulated sub-cellular movements are a fundamental aspect of all living cells and they rely on precisely controlled force generation mechanisms. How are forces imparted, monitored and corrected in response to heterogeneous biochemical and physical cues is a fascinating and challenging biological problem. We address these fundamental questions in the context of dividing human cells and apply the molecular knowledge on force generation and cell division to accelerate cytoskeletal drug discovery and drug resistance biomarker research. Defective force generation during cell division can lead to chromosomal instability and errors in the size, content and fate of daughter cells. Our research findings are therefore relevant to the understanding of irregular chromosome numbers (aneuploidy) and tissue disorganisation found in aggressive cancers and several age-related disorders. We combine single-cell microscopy with molecular and biochemical approaches. We collaboratively develop computational tools to extract single-cell and population metrics. These approaches form the platform for two streams of studies in our group: (i) To investigate how microtubules are correctly anchored, and subsequently how force generation powers the movements of chromosomes and the mitotic spindle, we use high and super-resolution live-cell imaging of human cells. (ii) To translate the basic knowledge on mitotic microtubule regulation into accelerating the discovery of novel microtubule perturbing drugs and drug resistance biomarkers, we have adopted bioinformatics approaches. For example, pharmacogenomics studies have allowed us to build transcriptional signatures to predict cells sensitive to Paclitaxel and to reposition two FDA-approved drugs as microtubule stabilisers (Splitomycin and Glipizide) through drug repositioning (Iorio et al., 2015). Bioinformatic analysis of human genetic variants of kinetochore and microtubule-associated proteins has led us to uncover protein residues or regions crucial for chromosomal and genomic stability, taking us a step closer to precision medicine (see CIVa database of variants screened from >150,000 healthy individuals and patients).Another wider aim of our research is to better understand how cells successfully position their spindle to ensure proper cell division in order to generate two genetically identical daughter cells from a single mother cell. Mispositioning of the mitotic spindle can lead to an incorrect plane of cell division and consequently altered stem cell fate and disorganized epithelia. In knockdown studies, our lab uncovered a novel role for MARK2 in maintaining the spindle at the cell’s geometric center. Following MARK2 depletion, spindles glide along the cell cortex, leading to a failure in identifying the correct division plane. For more information please visit our recent Publication List. By augmenting conventional image segmentation protocols with Deep Learning methods, we have developed the SpinX software to precisely track spindle movement through time. This computational approach allows us to monitor changes in spindle movements in response to drug treatments or protein depletions. The software is available on APEER and is being generalised further with ZeissTM UK and Germany. The software will help automate the analysis of spindle dynamics in CRISPR-edited iPSC lines expressing human genome variants of cell cycle regulators.
Elucidating how chromosomes captured along microtubule-walls are brought to microtubule-ends
Uncovering how cells distinguish chromosomes bound to microtubule-walls versus microtubule-ends
Determining the immediate and long-term impact of chromosome missegregation
Quantitative analysis of how cells pull and rotate their mitotic spindles
Microtubule-targeting drugs have been used for decades to treat aggressive cancers. Understanding how microtubule function is regulated during mitosis will help us improve microtubule-targeting drugs. Spindle microtubules (red in cartoon) capture chromosomes (blue) and pull them apart into two chromatids. Microtubule capture is facilitated by the Kinetochore (black-circles), a macromolecular structure that assembles specifically on the centromeric region of chromosomes. We would like to know how kinetochores tethered to microtubule-walls become tethered to microtubule-ends.
The kinetochore acts as a 'platform' that recruits checkpoint proteins, selectively, in the presence of erroneous or immature microtubule attachments. During end-on conversion, the cell has to dynamically distinguish an immature lateral attachment from a mature end-on attachment. How is this achieved? We study the various roles of the kinetochore to understand how it biochemically integrates dynamic temporal and mechanical events.
Errors in chromosome segregation can lead to chromosomal instability - a hallmark of cancers. Understanding the precise nature of lesions can help cancer diagnosis and targeted cancer therapies. By inducing different types of chromosome-microtubule attachment defects we ask how cells respond to different types of chromosome missegregation outcomes.
Astral microtubules interact with the cell cortex and they are pulled by cortical forces to rotate the mitotic spindle towards a pre-determined axis. In non-polarised tissue culture cells, the long-axis of the interphase cell acts as the predetermined axis. Spindles are also positioned parallel to the cell-adhesion substratum and maintained at the geometrical centre of the rounded up mitotic cell, allowing us to dissect force generation mechanisms that operate at the cell cortex. How do cells that lack polarity cues orient the spindle precisely within the 3-dimensional space of the cell? Do extracellular forces that change cell shape affect spindle position and cell fate?
Principal Investigator (Professor of Quantitative Cell and Molecular Biology and Director of Industrial Innovation at QMUL)
Viji M. Draviam is a Professor in Quantitative Cell and Molecular Biology at the School of Biological and Chemical Sciences, Queen Mary University of London and a Turing Research Fellow at The Alan Turing Institute. Her research interest is in the area of cell division and force generation, with a focus on the molecular basis for pathologies associated with cell division defects. To translate her group's research findings, Viji develops computational, molecular and optoelectronic tools with industry partners worldwide, Zeiss, Exscientia, MSD and Heptares. Viji leads the Center for Cell Dynamics, co-leads the AI for Drug Discovery UKRI/BBSRC-CTP and chairs the Research & Training Committee for BBSRC's flagship LIDo-DTP program. She started her independent research as a Cancer Research UK Career Development Fellow at the University of Cambridge and a Senior Fellow of Wolfson College, Cambridge. Draviam received a PhD from Trinity College, University of Cambridge and an MSc from the National Centre for Biological Sciences, Bangalore. Her post-doctoral work was with Peter Sorger at the Department of Systems Biology, Harvard Medical School and MIT, while her PhD work was with Jon Pines at the Gurdon Institute, University of Cambridge. She is a Nehru Scholar and fellow of the Cambridge Commonwealth Trust. She is the cofounder of CellCentives, an international clinical initiative to help eradicate Tuberculosis and a co-mentor of ENERGISE campaign that promotes STEM education among women students. Explore more .
Post-doctoral Research Associate
Parveen completed her PhD with Draviam Lab where she studied the biochemical interactions between an important kinetochore protein, Astrin, and PP1; specifically investigating its role in kinetochore-microtubule interactions. Parveen then returned as a post-doctoral research associate to continue her investigation on Astrin-PP1 interactions. Parveen uses Biochemistry, Molecular Biology, and Cell Biology tools to understand Astrin's biological role in cellular events including spindle movements, spindle orientation and the regulation of kinetochore-microtubule interactions. She has been a crucial member of the teams who worked towards several important papers published from the Draviam Lab. Parveen likes horse-riding, cycling, football, reading the history of civilisations, drawing and painting, gardening, and paper art.
Xinhong graduated from the joint undergraduate program launched by Nanchang University (China) and Queen Mary University of London (UK), with a clinical medicine and biomedical sciences double bachelor degrees. She is now a final-year PhD student at Queen Mary University of London. Her project is focused on detecting the molecular mechanisms driving aneuploidy in cancers, especially the molecular interactions involved during the kinetochore-microtubule attachment. Awards: CSC studentship (2019-2023)
Chris is a third-year PhD student within the BBSRC-funded London Interdisciplinary Doctoral Programme (LIDo). Before joining the Draviam lab, Chris obtained an integrated Masters (MSci) in Cell Biology from University College London (UCL). Being a cell biologist at heart, Chris is now looking to expand his scientific horizons by undertaking an interdisciplinary iCASE PhD project in collaboration with Image Solutions (IMSOL). His PhD project involves the implementation of the highly innovative Electrically Tunable Lens (ETL) technology for the meticulous investigation of spindle dynamics within the millisecond regime. In addition, Chris will be developing AI tools that would enable the automated analysis of the large volume of data generated. In his free time, Chris enjoys playing volleyball, philosophy, and cooking. Awards: BBSRC LIDo iCASE (2020-2024)
Saanjbati is a third-year PhD student in the Draviam laboratory. Saanjbati completed her MSc in Biomedical and Molecular Sciences Research at King’s College London. The main goal of her project is to study the interaction of the microtubule-associated protein, Astrin, with a serine/threonine phosphatase, protein phosphatase 1 (PP1). To address this question, she will use a combination of molecular and cell biology along with structural biology tools. By defining the structural and molecular basis of the Astrin-PP1 interaction, she aims to uncover how cells monitor their chromosome-microtubule attachment status and prevent chromosomal instability. In her free time, Saanjbati enjoys music, literature, reading, and travelling. Awards: QMUL Principal’s Studentship (2020-2024)
Catalina is a second-year PhD student at the School of Biological and Chemical Sciences, Queen Mary University of London (UK). Before starting her PhD, she achieved a bachelor's degree in Genomics Biotechnology from Universidad Autónoma de Sinaloa (México). Her BSc project involved the investigation of genetic events related to cancer. Subsequently, she worked at a molecular biology lab in Salud Digna (México) diagnosing SARS-CoV-II during the COVID-19 pandemic. Her research at the Draviam Lab is focused on studying microtubule interactions with the kinetochore during the cell cycle and how defects in this process drive aneuploidy in cancer. Awards: CONACyT scholarship (2021-2025)
Lisa is a first-year PhD student supported by a Zeiss-QMUL joint studentship. She completed her bachelor’s degree in biomedical studies at the University of Sussex in Brighton (UK) before joining the Draviam lab. Lisa is interested in cell cycle control research and its use in drug development. Her bachelor’s dissertation focused on how gene dependency correlations can be used to determine genes implicated in the cell cycle. In Lisa’s PhD project she will build new photoinactivation tools to control cytoskeletal force generation. Awards: Scholarship by “Studienstiftung des deutschen Volkes” (2020-2022) Zeiss-QMUL Joint studentship (2022-2025)
Siwen is a first-year PhD student on a CSC scholarship at the School of Biological and Behavioural Sciences, Queen Mary University of London and will work on human centromeric protein function. Before joining Professor Draviam's lab, Siwen obtained her MSc in cell biology at Zhejiang University studying karyotype changes associated with genetic reduction of CENP-A incorporation at centromeres in fission yeast. Awards: CSC scholarship (2022-2026)
Current position: Research Scientist at Newcastle University (UK)
Javad was a Postdoctoral Research Associate working on the KTP research project between Queen Mary University of London and Carl Zeiss Microscopy. His research focused on the generalisation of the SpinX software, which combines Deep Learning and 3D modelling methods to automatically analyse subcellular structures, subsquently facilitating application to cancer research and drug treatment. Before joining the Draviam lab, Javad was a Postdoctoral Research Associate at Imperial College London. His research focused on the image-based design of fuel cells and high-resolution X-ray imaging for determining the pore-scale wettability of porous media to validate pore-scale modelling. Moreover, he was a Postdoctoral Research Associate at the University of Manchester, investigating emulsion stability and behaviour using state-of-art microfluidics and imaging devices. Javad obtained his PhD in Chemical Engineering and Analytical Science from the University of Manchester. During his PhD, Javad utilised an array of theoretical, experimental, and imaging approaches to extend the physical understanding of foam generation, propagation and stability in pore-scale and bulk-scale. Javad got his MSc and BSc in Chemical and Petroleum Engineering at the Sharif University of Technology, the leading institution for engineering in his home country. Javad is now a Research Scientist at Newcastle University.
Current position: Postdoctoral Research Associate at Teeside University (UK)
Asifa completed her PhD project with the Draviam Lab from 2017-2021. Before joining the Draviam lab, she obtained an MRes in Oncology from the University of Manchester (UK). Asifa is a registered medical practitioner with the Pakistan Medical and Dental Council (PMDC), Pakistan, and has passed the UK medical licensing exams. Her PhD project looked on the role of kinetochore-bound microtubule-associated proteins in developing chromosomal instability in cancer cells. When not working, Asifa likes to travel and read. Asifa is now a Postodoctoral Research Associate at Teeside University in Middlesbrough.
Current position: Manager in AI & Data Analytics at Deloitte (Germany)
David completed his PhD through the BBSRC-funded London Interdisciplinary Doctoral Training Partnership Programme. As part of the scheme he undertook his first rotation with Prof Viji Draviam (Queen Mary University) and Prof Nishanth Sastry (King's College London; now University of Surrey), where he developed the SpinX Software to track 2D spindle movements in epithelial cells through conventional image processing methods. He then extended SpinX to 3D live-cell image analysis by combining state-of-the-art Deep Learning and 3D mathematical object modelling to delineate 3D spindle movements. Having been trained as a Statistician and Computer Scientist (University of Tuebingen and University of Bremen, Germany) prior to coming to London, he sees himself as one who combines Computer Vision concepts, biological techniques and statistical ideas together to seek advances to address the ultimate question of how subcellular changes behave in cells from a quantitative perspective. Beside his research David enjoys coding, composing orchestral music, philosophy and playing handball. David is now a Manager in AI & Data Analytics at Deloitte in Munich. Awards: BBSRC LIDo DTP (2016-2020) LSI Showcase Award (2017) Nominated for QMUL Research Impact Award (2021)
Current position: EMBO Long-Term Postdoctoral Fellow at Max Planck Institute (Germany)
Duccio graduated from the University of Cambridge (UK) - affiliated to Robinson College. He continued his research in the Draviam Lab as a BBSRC-funded post-doc. Duccio obtained his MSc in Molecular Genetics at the University of Leicester (UK) and his BSc in Biological Sciences at the Università degli Studi di Firenze (Florence, Italy). Duccio's PhD project focused on how kinetochores captured along the walls of microtubules become tethered to the ends of microtubules, and how this process is regulated and stabilised by the kinase-phosphatase counteraction at the outer-kinetochore level. Duccio was awarded an MM in clarinet performance before beginning his biological studies. When not working in the lab, Duccio still plays the guitar and enjoys street-skating with inline skates. Duccio is now an EMBO Long-Term Postdoctoral Fellow at the Max Planck Institute in Dortmund.
Current position: Postdoctoral Research Fellow at Wellcome Trust Sanger Institute (UK)
Dr Dijue Sun was a visiting postdoctoral research scientist at the Draviam lab. She is a cell biologist specialised in chromosome segregation and DNA double-strand breaks in meiosis. During her PhD, she designed a yeast artificial chromosome transfer method to study non-exchange chromosome segregation in meiosis using live-cell imaging. After her PhD, she went on to study how proteins affect the adaptive immune system and cell signalling at the Williams Harvey Research Institute (QMUL), which led to a first author paper in Cell Reports (2019). After one period of postdoctoral study, Dr Sun took a gap to raise her children. During the period of working with the Draviam Lab, Dr Sun helped in developing Deep Learning Methods for the automated analysis of mitotic spindle movements. She has been awarded a Janet Thornton return Fellow at Sanger institute, where she will be studying saturated genome editing on DNA Mismatch repair proteins that affect Lynch Syndrome.
Maddy completed her PhD project with the Draviam Lab from 2016-2020. Maddy investigated the cellular consequences of kinetochore lesions, with a particular focus on DNA damage. She completed her undergraduate degree at Newcastle University in Biomedical sciences in 2014. Maddy also worked in an NHS diagnostic lab before starting her PhD. Outside of the lab Maddy enjoys skiing and reading.
Current position: Senior Account Executive at GCI Health (UK)
Tami Kasichiwin undertook an intergrated Masters in Biochemistry (2014-2018) at Queen Mary University of London. Her previous work focused on pharmacology and structural biology, specifically the mode of action of COX inhibitors. Having a strong interest in the cell cycle and proteins, her MSci project was to investigate mechanisms involved in microtubule formation and stability. Outside the laboratory, her hobbies include badminton and baking.
Nadia Osumanu completed her undergraduate research project for an integrated Masters in Biochemistry with the Draviam lab in 2018. As part of her undergraduate research project she used NMR to investigate the substrate recognition mechanism of the L. pneumophila secretion system. In her free time she loves to read, listen to Ted talks and podcasts and is currently learning Arabic.
Current position: Lecturer at Universiti Brunei Darussalam (Brunei)
Ihsan obtained a BSc in Biochemistry at the University of Bristol before moving to Imperial College London to complete an MSc in Human Molecular Genetics. For her PhD project Ihsan investigated how MARK2/Par1 kinase controls spindle movements. She also contributed to automated analysis of spindle movements in human epithelial cells. Ihsan is now back in her home country, Brunei Darussalam, as an Assistant Professor of Haematology.
Current position: Clinical Data Analyst at GSK (UK)
Naoka completed her MRes in Cell biology at the Wellcome Centre for Cell biology in the University of Edinburgh after obtaining a BSc in Biology from the University of Nottingham. As part of her PhD project, Naoka investigated how microtubule-ends recruit distinct protein complexes during specific stages of mitosis. Following her PhD, Naoka became a post-doctoral fellow at the Barts Cancer Institute in London.
Current position: Research Fellow at National Cancer Institute at The National Institutes of Health (US)
During his time at the Draviam lab (2011-2015) Roshan studied the molecular mechanisms involved in ensuring proper kinetochore-microtubule attachments. Roshan's work showed how chromosomes bound to the walls of microtubules convert their lateral interaction with walls into an end-on interaction with microtubule ends (Shrestha and Draviam, Current Biology, 2013). Roshan worked on the anti-microtubule drug discovery project as well. Roshan received an MRes in Medical Biosciences from Northumbria University, UK. As a part of his MRes thesis he completed a research project based on DNA repair proteins and Topoisomerase II. During this work, Roshan investigated the in vivo protein-protein interaction of human DNA Topoisomerase II with DNA repair proteins, Meiotic Recombinant 11 and Tyrosyl DNA Phosphodiesterase.
Current position: Principal Data Scientist - Imaging at AstraZeneca (UK)
Adam was a postdoctoral research associate investigating the effect of external factors on mitotic spindle orientation. This work was a collaboration with Professor Athene Donald in the sector of Biological and Soft Systems (BSS) at the Department of Physics, University of Cambridge. The project combined high-throughput microscopy with the development of automated image processing tools to measure and model 3D spindle orientation in non-polarised cells. Adam generated the first version of Spindle3D. Adam then worked with Professor Jonathan Chubb's group at UCL.
Current position: Principal Investigator at the Institute of Molecular and Cell Physiology, Hannover Medical School (Germany)
Arnab worked on understanding the regulation and checkpoint role of TAO1 kinase with the help of high-throughput immunoprecipitation and mass spectrometry tools. Arnab then worked with Professor Stefan Muller's group, IBCII.
Current position: Post-doctoral researcher at Barts Cancer Institute (UK)
Judith worked at the Draviam lab for her final year master's research project, University of Groningen (2011-2013). Judith helped us with yeast two-hybrid studies of interactions between the KMN network and microtubule plus-end associated proteins. Judith then went to work with the Foijer group at the University of Groningen for a PhD in Oncology and Cancer Biology.
School of Biological and Chemical Sciences
Queen Mary University of London
Mile End Road
E1 4NS London
Prof Viji M Draviam
Telephone: +44 (0)20 7882 5020