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 force generation controlled to power the movements of chromosomes and mitotic spindle, we use high-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 perform pharmacogenomics studies. We are currently refining transcriptional signatures that can predict cells sensitive to Paclitaxel. Visit ongoing research projects for more information.
We enjoy exploring mechanical force generation events that orchestrate cell division in human cells:
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 targetting drugs have been used for decades to treat aggressive cancers. Understanding how microtubule function is regulated during mitosis will help us improve microtubule targetting 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 to 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 targetted 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 (Associate Professor at QMUL)
Viji M. Draviam is an associate Professor in Molecular and Cell Biology at the School of Biological and Chemical Sciences, Queen Mary University of London. Her research interest is in the area of cell division, with a focus on the molecular basis for pathologies associated with cell division defects. 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 Ph.D. from Trinity College, University of Cambridge and an M.Sc. from 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, and 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 .
Duccio graduated from the University of Cambridge (UK) - affiliated to Robinson College. He continues his research in Draviam Lab as a BBSRC-funded post-doc Duccio did 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 is 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 kinase-phosphatase counteraction at the outer-kinetochore level. Duccio has a MM in clarinet performance awarded before starting his biological studies. When not working in the lab, Duccio still plays guitar and enjoys street-skating on inline skates.
Maddy is a fourth year PhD student at QMUL, whose project looks into 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. After which she worked in an NHS diagnostic lab before then starting her PhD. Outside of the lab Maddy enjoys skiing and reading.
David Dang is a third-year PhD student in the BBSRC-funded London Interdisciplinary Doctoral Training Partnership Programme. As part of the scheme he completed his first rotation with Dr Viji Draviam (Queen Mary University) and Dr Nishanth Sastry (King's College London), where he developed the spinX Software to track spindle movements in epithelial cells. Currently, he is working on a feature in spinX Software to expand the application field on 3D live-cell image analysis as an enlightening challenge to investigate spindle movements with the aid of sophisticated and intricate web of information embedded in the images through time lapse and dimensions. Having been trained as a Statistician and Computer Scientist (University of Tuebingen and University of Bremen, Germany) prior to coming to London, now he sees himself as who combines Computer vision concepts, biological techniques and statistical ideas together to seek advances to address the ultimate question how subcellular changes behave in cells from a quantitative perspective Explore more. Beside his research David enjoys coding, composing orchestral music, philosophy and playing handball.
Asifa is a third-year PhD student at Queen Mary University of London (UK). Before joining Draviam lab, she did an MRes in Oncology from University of Manchester (UK). Asifa is a registered medical practitioner with Pakistan Medical and Dental Council (PMDC), Pakistan and has passed UK medical licensing exams. Her PhD project looks at role of kinetochore bound microtubule associated proteins in developing chromosomal instability in cancer cells. When not working, Asifa likes to travel and read.
Parveen is a second-year IDB-funded PhD student at Queen Mary University of London (UK) studying the role and regulation of PAR3 during mitosis. Parveen uses Biochemistry and Molecular Biology tools to understand how the Phosphatase PP1 interacts with cytoskeletal and cortical proteins during mitosis.
Tami Kasichiwin is currently undertaking an intercalated Masters in Biochemistry 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 is to investigate mechanisms involved in microtubule formation and stability. Outside the laboratory, her hobbies include badminton and baking.
Nadia Osumanu is in the process of completing an integrated Masters in Biochemistry. 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 times she loves to read, listen to Ted talks and podcasts and is currently learning Arabic.
Ihsan Zulkilpi obtained a B.Sc. in Biochemistry at the University of Bristol before moving to Imperial College London to complete an M.Sc. in Human Molecular Genetics. For her PhD 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.
Naoka Tamura completed her Masters by research in Cell biology in Wellcome trust of Cell biology in the University of Edinburgh after obtaining a B.Sc. Biology in the University of Nottingham. As part of her PhD project, Naoka investigated how microtubule ends recruit distinct protein complexes during distinct stages of mitosis. Naoka is now a post-doctoral fellow at the Barts Institute in London.
Roshan Shrestha is a Research assistant and graduate student studying the molecular mechanisms involved in ensuring proper kinetochore-microtubule attachments. Roshan's work recently 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, 2013, under review). Roshan works on the anti-microtubule drug discovery project as well. Roshan received his Masters degree (by Research) 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.
Adam Corrigan was a postdoctoral research associate investigating the effect of external factors on mitotic spindle orientation. This work is a collaboration with Professor Athene Donald in the sector of Biological and Soft Systems (BSS) at the Department of Physics, and combines high-throughput microscopy with the development of automated image processing tools to measure and model the 3D spindle orientation in non-polarised cells. Adam generated the first version of Spindle3D. Adam is currently working with Dr. Jonathon Chubb's group, UCL.
Arnab Nayak worked on understand the regulation and checkpoint role of TAO1 kinase with the help of high-throughput immunoprecipitation and mass spectrometry tools. Arnab is currently working with Prof. Stefan Muller's group, IBCII.
Judith Simon worked for her final year master's research project, University of Gottingen. Judith helped us with yeast 2 hybrid studies of interaction between KMN network and microtubule plus-end associated proteins. Judith is currently working in Foijer group at the University of Groningen.
School of Biological and Chemical Sciences
Queen Mary University of London
Mile End Road
E1 4NS London
Dr Viji M Draviam
Telephone: +44 (0)20 7882 5020