Genome engineering and maintenance experts

Dr Rhona Anderson Qualifications: FHEA, Brunel University London PhD, Brunel University London MSc, University of Aberdeen BSc (Hons), University of Strathclyde Professional Qualification Certified Clinical Cytogeneticist (ACCCC) Appointments 2019: Reader in Radiation Biology, Brunel University London, UK 2016: Senior Lecturer in Biomedical Sciences, Brunel University London, UK 2005: Lecturer in Biomedical Sciences, Brunel University London, UK 1996 - 2005: Research Associate, MRC Radiation and Genome Stability Unit, Harwell, UK We are interested in how exposure to ionising radiation, from a variety of occupational, medical and environmental sources can lead to genomic damage, and the mechanisms of how this cellular damage may lead to adverse human health effects. Our current research projects can be grouped broadly as (1) Genetic markers of radiation exposure (2) understanding health risks of exposures (3) Health and Wellbeing and, (4) Education and Engagement. Full list of projects: Research Projects – Centre for Health Effects of Radiological and Chemical Agents (chrc4veterans.uk) Radiation biology, radiation cytogenetics, Low dose radiation research Teaching Responsibilities: BB3091 Final year Project Coordinator Department of Life Sciences Director for Postgraduate Research MSc Radiation, Toxicology and Pollution

Dr Sara Anjomani Virmouni Sara was educated at the University of Tehran, where she was awarded a Bachelor degree in animal sciences with first class honours in 2008. She moved to the Biosciences Division at Brunel University London to undertake her MSc in Molecular Medicine and Cancer Research. In 2011, Sara was awarded a scholarship by the School of Health Sciences and Social Care, Brunel University London to investigate Friedreich’s ataxia (FRDA) disease mechanisms using FRDA mouse models and cells under the supervision of Dr Mark Pook. She finished her PhD in 2013 and was awarded Vice Chancellor's best doctoral research prize. She continued her work as a Postdoctoral Research Fellow at Brunel University London to study the efficacy and tolerability of histone methyltransferase (HMTase) inhibitors in FRDA. Sara then joined the Institute of Cancer Research (ICR) as a Postdoctoral Research Fellow in 2015 to study the signaling and metabolic networks in breast cancer. In 2018, she was awarded a research grant from Friedreich’s Ataxia Research Alliance (FARA) and joined Brunel University London as a Principal Investigator to investigate the metabolic signatures of FRDA. Subsequently, she was appointed as a lecturer in Biosciences. Her research continues to investigate FRDA disease pathogenesis and therapy and identify the most effective therapy for FRDA. The Ataxia Research Group investigates molecular disease mechanisms and therapy for the inherited disorder, Friedreich’s ataxia (FRDA). Currently, the lab is focused on five projects: Metabolomics analysis of FRDA cells Proteome/phosphoproteome analysis of FRDA cells Cell and gene therapy for FRDA Therapeutic potential of different antioxidants in FRDA Development and characterisation of GAA repeat-based FRDA transgenic mouse models Team: Senior Research Fellow Dr Sahar Al-Mahdawi Postdoctoral Researcher Dr Saqlain Suleman PhD Students Mr Fred Edzeamey Ms Zeynep Ulukutuk MS Zenouska Ramchunder Neurodegenerative diseases, Friedreich’s ataxia, Epigenetics and Metabolomics

Professor Amanda Harvey Qualifications: PhD - Studies into the growth survival and cell death of cancer cell lines, University of Sheffield Medical School BSc (Hons) Biochemistry - University of Wales, College of Cardiff Professional development 2008: PGCert TLHE 2006: Enrolled PG Cert Brunel University London 2001: College Certificate in Teaching Skills for Higher Education, Royal Holloway University of London Current Research Interests and Expertise Breast cancer biology Cell Signalling Mechanisms of therapeutic resistance Assessment of alternative therapies Resistance to anti-cancer treatment is a major issue for cancer patients. Our work focuses on (i) understanding the contribution that cell signalling plays to the development of therapeutic resistance in breast cancer, (ii) identifying new therapeutic targets and (iii) discovering potential new treatments. Teaching Responsibilities: Co-ordination Roles BB3733 Molecular Pharmacology and Toxicology BB5500 MSc Dissertation Contribution to other modules BB3091 Final Year Project BB3704 Biology, Genetics and Treatment of Cancer BB2802 Primary Literature Interrogation and Synthesis (Assessment) BB2804 Data Analysis and Presentation (Assessment) BB5514 Cell Signalling and Cancer BB5506 Biology Genetics and Treatment of Cancer BB5501 Research Planning (Assessment) BB5500 MSc Research Dissertation Academic appointments 2015: Senior Lecturer in Biomedical Sciences, Division of Biosciences, College of Health and Life Sciences 2006: Lecturer in Biomedical Sciences, Division of Biosciences, School of Health Sciences and Social Care 2000-2006: Post-doctoral researcher, School of Biological Sciences, Royal Holloway University of London 1998-2000: Post-doctoral researcher, Human metabolism and Clinical Biochemistry, University of Sheffield Medical School 1997-1998: Research Assistant, Clinical Sciences Centre, University of Sheffield 1993-1997: Robert-Boulcher PhD scholarship, Institute for Cancer Studies, University of Sheffield Medical School

Dr Victor Hernandez Over the last ten years I have focused my career in studying of the molecular mechanisms behind human genetic disorders such as ciliopathies and craniofacial anomalies. The final aim of my research is to find a therapeutically solution for these untreatable disorders and cure or alleviate their symptoms. My interest have been focused in Bardet-Biedl Syndrome (BBS), a multi-syndromic disorder with characteristic truncal severe obesity, brain anomalies and retinal degeneration. At a molecular level, I have introduced the concept that the actin cytoskeleton is linked to cilia and play an important cellular role in ciliopathies such BBS. My research have contributed to the development of animals models to study ciliopathies including zebrafish and BBS mouse models. My work with these mouse models have been an important tool to comprehend the biological progression of the retinal degeneration and obesity. I have help to broad our understanding of the origins of the retinal and obesity phenotypes in BBS, proving how they show a great variability within the penetrance of the phenotypes which is important to understand in the scientific community want to test possible therapies on them. However, on top of all these efforts I consider that my most important contribution is the development of gene therapy solutions to treat obesity and retinal degeneration in BBS. In collaboration with many groups I have proven that the use of adeno-associated virus (AAV), as vectors to deliver corrected copies of BBS genes, are able to prevent retinal degeneration, obesity and CNS malformations in our BBS mouse models. This have led to a patent application, gene therapy for ciliopathies, which have one single aim; attract funding to start clinical trials in BBS patients. At the beginning of this journey we knew little over the function of the BBS genes, and we are now in a situation where a therapy appears as a real possibility. This is pushing me forward to improve our knowledge brain, obesity and retinal defects in ciliopathies and BBS, to test our therapies and all of this should be achieved using the best collaborative efforts and state of the art technology. Research Areas Developing gene therapies for Bardet-Biedl Syndrome My main interest is developing different gene transfer techniques to treat Bardet Biedl syndrome (BBS). I use BBS murine models to restore gene function with the help of different serotypes of adeno-associated virus (AAV) expressing wild-type BBS genes under the control of different promoters. The results show we results a capacity to rescue the affected tissues and we are now proceeding to developed clinically relevant products to start clinical trials. Molecular mechanisms behind ciliopathies My research also focuses on the mechanisms by which primary cilia are regulated by genes mutated in ciliopathies and BBS. We are studying cilia formation and regulation in cellular and animal models lacking BBS gene function to understand how their interactions influence cilia function. I am interested in understanding how ciliary related gene expression is regulated in a different way in affected tissues and how this affect the downstream molecular pathways. In all our BBS mouse models, retinal degeneration and truncal obesity are consistent progressive phenotypes. Understanding how retinal degeneration occurs in BBS mouse models is an important step to find a possible clinical response to these degenerative phenotypes. Studying the cellular mechanisms linked in the late onset cell death of the photoreceptors or the hypothalamic regulation of obesity will improve the capacity of creating Ciliopathies Bardet-Biedl syndrome Adeno-asscoiated virus (AAV) Gene Therapy Ciliary biology

Dr Thomas Hofken Qualifications: 1998: PhD, University of Marburg and University of Bochum (Germany) 1993: Diplom in Biology, University of Bochum (Germany) Academic Appointments Since 2010: Lecturer in Biomedical Sciences, Brunel University London 2004-2010: Lecturer, University of Kiel (Germany) 2002-2004: Postdoctoral Scientist, Paterson Institute for Cancer Research, Manchester 2000-2002: Postdoctoral Scientist, Beatson Institute for Cancer Research, Glasgow 1998-1999: Postdoctoral Scientist, University of Bern (Switzerland) Our group is interested in the regulation of fundamental cell biological and biochemical processes. The budding yeast Saccharomyces cerevisiae is an ideal system to study these processes due to the ease of manipulations and the high degree of conservation from yeast to man. We are particularly interested in p21-activated kinases (PAKs). These key signalling molecules have a surprisingly wide range of functions. In budding yeast, three different PAKs can be found: Ste20, Cla4 and Skm1. We are interested in the identification and characterisation of novel functions of PAKs, in particular of Ste20. We have previously shown that Ste20 regulates mitotic exit, sterol biosynthesis and uptake, and V-ATPase activity. At the moment we further investigate the role of Ste20 and Cla4 in metabolism and gene expression. Teaching Responsibilities: Study block co-ordinator for BB1702 Biochemistry: Structure and Function Assessment block co-ordinator for BB1801 Research and Communication Skills BB1803 Practical Skills 2: Biochemical Analysis

Dr Emmanouil Karteris Dr Manos Karteris graduated with a BSc (Hons) in Medical Biochemistry from the University of Surrey in 1995. He then was awarded an MSc with Distinction in Medical Genetics with Immunology from Brunel University London in 1996 and completed his PhD in Molecular Endocrinology from the University of Warwick in 2000. He then undertook post-doctoral appointments at the University of Warwick, including a prestigious VIP Research Fellowship from the Wellcome Trust. He was appointed as Lecturer in Endocrinology at the University of Warwick from 2005-2006 and then he transferred to Brunel University London as a Lecturer in Biomedical Sciences in June 2006. Currently he is a Reader in the Division of Biomedical Sciences. Dr Karteris is the Departmental Director International. Role of endocrine disrupting chemicals in the feto-placental unit Detection and characterisation of circulating tumour cells Use of liquid biopsies as cancer biomargers of diagnostic and prognostic value Development of fetal-placental 3D cultures as a screening platform for EDCs Dr Karteris has a long standing interest in mTOR signalling with emphasis in reproductive endocrinology and ovarian cancer. His lab is also active in the field of biomarker development using liquid biopsies. Dr Karteris has a recognized publication record in receptor biochemistry and cell signalling. He has published 89 research manuscripts, presented over 100 research abstracts in leading national and international conferences. Many of these papers are generating a strong and influential impact not only to the biomedical field (h index; 31) but also to the society as they deal with topical issues such as effects of stress during pregnancy. Moreover Dr Karteris has established collaborations with leading authorities in their fields and has been successful in obtaining research grants at national and international level. Teaching Responsibilities: Co-ordination Roles Study Block co-ordinator for BB3714 Endocrine Disorders Contribution to other modules BB3091 Final Year Project BB2802 Primary Literature Interrogation and Synthesis (Assessment) BB2804 Data Analysis and Presentation (Assessment) BB5514 Cell Signalling and Cancer BB5500 MSc Research Dissertation

Dr Annabelle Lewis I am a lecturer in biomedical sciences and run a research laboratory. My research interest is cancer genetics and gene regulation, focusing on colorectal cancer. We use cell lines and animal models to study how common variants in the human genome affect the expression of key cancer genes, and increase the risk of an individual developing cancer. Our lab focusses on finding out how non-coding SNPS associated with colorectal cancer (CRC) affect gene expression and cancer pathways. A major project within the lab involves a SNP in the promoter of the mismatch repair pathway gene MLH1. MLH1 is disrupted in about 15% of colorectal cancers, termed MSI+ cancers. These tumours generally show a good prognosis at early stages but have a poor response to some common chemotherapy treatments. The SNP variant, rs1800734, near MLH1 is strongly associated with increased risk of MSI+ colorectal cancer and also linked with increased DNA methylation and MLH1 gene repression. Our aims are to investigate and correlate allele specific MLH1 expression, DNA methylation and protein binding in the region. To do this we are developing isogenic colon cancer cell lines, and we will compare these with normal and cancer patient samples. In addition we plan to manipulate MLH1 expression and methylation independently in our cell line systems to investigate their reciprocal interactions and any allele specific effects of the SNP on this interplay. Finally we develop transgenic mouse models modifying the SNP and investigate its effect on mice with a CRC predisposition. We are also interested in SNP variants associated with colorectal cancer risk in the POLD3 and CHRDL2 loci. POLD3 is a component of the Pol δ polymerase which functions in both replication and repair. However, its role in colorectal cancer is largely unexplored. CHRDL2 is an antagonist of the bone morphogenetic protein pathway and while it has no known role in colorectal cancer similar pathway antagonists are known to have a major influence on intestinal tumour initiation. We are using in vitro and in vivo model systems to investigate the role of POLD3 and CHRDL2 in cancer pathways. In parallel we are working to identify the causative SNP and regulatory element(s), and the mechanisms by which they influence cancer initiation or progression. Many common genetic variants that are associated with increased risk of cancer have been found in recent years. However these variants, known as single nucleotide polymorphisms (SNPS), most commonly lie outside of coding regions and often some distance away from any gene. There are over 100 variants associated with colorectal cancer risk. The mechanisms by which these SNPs exert their effect on cancer initiation or progression are currently poorly understood, although it is likely that they modify the expression levels or pattern of specific genes. Translating this growing resource of genetic data into information that is useful in the cancer clinic is both important and challenging.

Dr Ruth Mackay Dr Mackay is a Mechanical Engineer with a particular interest within the biomedical field. She gained her undergraduate degree from the University of Dundee in 2007 in Mechnical Engineering. This was followed by a her PhD Micro-electromechanical-systems in 2011, also at the University of Dundee, funded by a CASE grant from the EPSRC with IDB Technologies. She moved to Brunel in 2011 to work as a Research Fellow on a tanslational MRC grant developing point of care devices. She became a lecturer at Brunel in 2015. Her research focuses on organ-on-a-chip tecnologies for women's health, low cost point of care diagnostic devices and prosthetics. She teaches within the areas of Finite Element Analysis and Medical Device Engineering. Dr Mackay's primary research focus is within the field of Organ-on-a-Chip (OOC). Within the group she researches the development of microfluidic devices, manufacturing methods, cell scaffold facbrication and electronic control of the systems. The OOC group at Brunel University London (www.bruneldoclab.com) incorporates toxicologists, engineers, life scientists and bioinformaticians. The group’s research focuses on developing alternative systems to study women’s health issues, such as cancers, pregnancy outcomes and sexually transmitted infections. We are currently working on systems that replicate female organs (vagina, ovaries, placenta and breast) to better understand initiation, progression diagnosis and treatment of women’s diseases and disorders. Her other research interests include low cost, point of care diagnostics, prosthetics and soft robotics Organ on a Chip Low cost diagnostics Microfluidics Prosthetics Soft Robotics ME3622 Mechanical Engineering Structures ME3626 Vehicle Structures and FEA ME5678 Medical Device Engineering ME5692 Group Project (MEng)

Dr Evgeny Makarov Qualifications: PhD, Molecular Biology – Institute of Molecular Biology and Genetics, Kiev, USSR MSc, Biophysics – Leningrad Polytechnical University, Leningrad, USSR My research interests are in the field of precursor messenger RNA (pre-mRNA) splicing. Pre-mRNA splicing is a cellular process in which non-coding sequences (introns) are removed and coding sequences (exons) are joined together to generate mRNA for protein production. Pre-mRNA splicing is somewhat similar to film editing: if it is not done properly, two unmatched scenes may be stitched together in one episode, which would not make sense. In splicing, if exon-intron boundaries (splice sites) are not correctly identified, the wrong mRNA will be produced. From this, a faulty protein will be synthesised and this may cause disease. To extend the analogy, a film scenario is dramatically changed by the selection of scenes; by the same token, in a living cell, pre-mRNA can be processed in different ways via the alternative use of different splice sites. This phenomenon is called alternative splicing and allows the production of several proteins from a single gene. I am currently focused on the study of disease-associated alternative splicing. The major ongoing project is on the study of the ageing-related pre-mRNA splicing of human LMNA gene, encoding lamin A and C proteins, and especially, its aberrant splicing that causes the premature ageing of Hutchinson Gilford Progeria Syndrome patients. The aim is to identify the proteins modulating the specific splicing outcomes which, in turn, are likely to affect the speed of the ageing process. In this respect, the pharmaceutical targeting of the proteins identified in the proposed research -- inhibition of their function by small interacting molecules -- may lead to the discovery of novel drugs capable of slowing the ageing process. The other ongoing projects are: (i) The hTERT alternative splicing regulation as a potential cancer therapeutic modality; (ii) Exosomes as the delivery vehicles for therapeutic RNAs; (iii) Extracts from fruit soursop (Annona muricata) as a source of anti-cancer agents. Gene expression; RNA processing; precursor messenger RNA (pre-mRNA) splicing; exosomes; natural products as a source of anti-cancer agents. Teaching Responsibilities: Module co-ordinator BB3710 - Methods in Forensic Investigation BB5704/BB5804 - Scientific Communication Other Teaching Responsibilities: Academic appointments 2007: Lecturer, Division of Biosciences, School of Health Sciences and Social Care, Brunel University London. 2005-2007: Research Associate, Department of Biochemistry, University of Leicester. 1998-2000: Post-doctoral researcher, Max-Planck-Institut für Biophysikalische Chemie, Göttingen, Germany. 1997-2000: Post-doctoral researcher, Institut für Molekularbiologie und Tumorforschung, Philipps-Universität, Marburg, Germany 1994 -1997: Research Associate, Department of Biochemistry, University of Leicester,UK 1993 -1994: CNRS researcher, Laboratoire de Génétique Moléculaire, Ecole Normale Supérieure, Paris, France 1991 -1993: Post-doctoral researcher, Department of Biological Chemistry, School of Medicine, University of California, Davis, USA. 1990 -1991: Post-doctoral researcher, Department of Molecular Microbiology, School of Medicine, Washington University, St. Louis, USA 1980 -1990: Research scientist, Department of Molecular and Radiation Biophysics, Leningrad Nuclear Physics Institute, Gatchina, USSR

Dr Annette Payne Having gained a PhD in 1992 in Molecular Biology from the Royal Postgraduate Medical College, University of London I undertook two post doctorial positions; the first at the National Heart and Lung Institute, University of London researching the molecular biology of atherosclerosis, the second at The Institute of Ophthalmology, University of London researching the molecular genetics of retinal diseases, before joining Brunel University London Dept. of Bioscience in 2000. I have since transferred to the Department of Computer Science as my interest in computational biology grew. I have now additional research interests in technology and computer assisted learning, and the use of technology to monitor and manage medical conditions. I have over 100 peer reviewed publications many of them can be found on my Research Gate profile at These publications highly cited over 2000 times by other researchers (RG score of over 35 most months, and a ISI h-index of 31). I a Research Interest Score that is higher than 92% of researchers in my field. Disciplines Data Mining Human-computer Interaction Computing in Mathematics, Natural Science, Engineering and Medicine Bioinformatics Molecular Biology Systems Biology Skills and expertise Human Genetics Next Generation Sequencing Gene Expression Genomics Transcriptomics E-Learning Blended Learning TEL Synthetic Biology Bioinformatics and Computational Biology My research interests are divided into two areas: 1. Computational and systems biology, including machine learning, bioinformatics and medical informatics. 2. Technology assisted learning, including e-learning, blended learning, cross discipline use of technology in the arts and design. As well as supervising PhD students in my areas of interest I teach the following modules: Ethics and Governance Data and Information Management Group projects Dissertations

Dr Christian Rudolph Cell division is one of the most fundamental processes in biology. Thousands of proteins have to be made successfully to enable accurate duplication of the genetic information, segregate duplicated chromosomes into daughter cells and to complete cell division. Our lab aims to provide important new insights into how the genome can be duplicated with high accuracy, how damage to the genome can be recognised and repaired and what consequences arise if these processes fail. We use a range of advanced molecular cell biology and genetics techniques for traditional as well as new experimental approaches to study DNA replication and chromosome dynamics, conflicts between DNA replication and transcription, CRISPR-Cas systems and their impact on DNA replication and genome stability and how all these systems contribute to shape the overall architecture of bacterial chromosomes. The Rudolph Lab is involved in a variety of active research areas. My long-standing interests in DNA replication and genomic stability have led me to focus on how these factors impact DNA repliation, chromosome dynamics and chromosomal architecture. Currently we have a number of active projects: − We investigate DNA replication dynamics in Escherichia coli with a particular focus on the termination aspect of DNA replication. We demonstrated for the first time that RecG helicase can process intermediates that form when replication complexes fuse. Our recent findings highlight that a surprising number of proteins act to process replication termination intermediates, thereby avoiding severe problems for cell-cycle progression and genome stability. − We are investigating replication-transcription conflicts at a single molecule level in collaboration with Prof. Mark Leake (York University). − In collaboration with Ed Bolt (University of Nottingham) we investigate the role of CRISPR-Cas systems on DNA replication and genome stability. − We are investigating how all of the above system contribute towards shaping the overall architecture of bacterial chromosomes. The research in my lab was supported by funds from the Leverhulme Trust, the Royal Society, and BBSRC and Brunel University. Our current work is supported by funds from the BBSRC. − Molecular cell biology − Genomic stability − DNA replication dynamics Escherichia coli − CRISPR-Cas and the interaction of the CRISPR-Cas system with DNA replication and genome stability in E. coli. − Investigations into conflicts between DNA replication and transcription in living cells at a single molecule level. − Investigations into how the above systems contribute to shaping the architecture of bacterial chromosomes.

Dr Elisabete Silva Research Activities: My main research interests are focused on addressing the hypothesis that the human total body burden of endocrine disrupters is implicated in hormone related diseases, such as breast cancer. Work addressing this issue was carried out during my PhD and postdoctoral fellowship (as part of the EU-funded project EDEN) and included predicting and assessing the estrogenic effects of multi-component mixtures of toxicants representative of human exposure, evaluating low-dose effects and determining combination effects of different classes of environmental contaminants (eg. pesticides and heavy metals). Based on the observed interactions between estrogenic compounds, I developed a personal interest in the mechanisms of action of estrogens in the breast, and more specifically, in breast carcinogenesis. This interest has been reflected in my work on the effects of estrogens on growth factor signalling pathways and genomic instability. Since 2008, I have been involved in developing and optimising alternative in vitro models which recapitulate the features of the breast and allow the evaluation of potential neoplastic transformations of the mammary gland. By utilising these systems, which include three-dimensional co-cultures of breast cells and organ-on-a-chip approaches, I study the effect of steroidal and environmental estrogens on breast glandular structure, morphogenesis and carcinogenesis. The work described here is carried out in collaboration with Dr Ruth Mackay from the College of Engineering, Design and Physical Sciences and Drs Emmanouil Karteris and Ashley Houlden, from the College of Health and Life Sciences at Brunel Univeristy. Building on my expertise on mixture assessment, in 2008, I started collaborating with Dr H Carmo, at the University of Porto, Portugal in a project in forensic toxicology studying the toxicological interactions between amphetamine designer drugs. In this work, the concepts previously utilised for the prediction and assessment of mixtures of environmental estrogens were applied to improve the understanding of the potential toxicological interactions between amphetamines, in the context of polydrug abuse.

Dr Cristina Sisu Dr Sisu joined Brunel University as Lecturer in Genomic Data Analytics in April 2017. Prior to that, she studied Chemical Engineering first at University “Politehnica” Bucharest and then at University “Politehnica” Timisoara in Romania, followed by an MSc in Molecular Sciences at Wagennigen University, The Netherlands and a PhD in Bioinformatics at University of Cambridge. Next, she moved to USA as a post-doc at Yale University in the lab of Mark Gerstein. Dr Sisu’s current research focuses on the study of pseudogenes from both an evolutionary perspective but also as key players in various disease. Dr Sisu is also the chair of the Early Career Lectures in Bioscience at HUBS (Royal Society of Biology). For a complete list of publications see I am the lead for the Introduction to data analysis HEFQ level 4 Biomedical Sciences (BB1719) and the lead for the Introduction to Bioinformatics HEFQ level 5 Life Sciences (LS2702 & LS2802). I am also teaching Transcriptomics and RNAseq analysis as part of the MSc module BB5707. Postdoctoral positions Applications for postdoctoral positions are considered on a rolling basis. Applicants should hold a PhD or be in their last six months of doctoral studies in Computer Science, Physics or Biology and should have a strong computational background. Currently there are no funded positions available. However, we are happy to support your application for an independent fellowship. If interested, please contact Dr Sisu directly sending as attachment a cover letter, CV and contact details of 3 references from supervisors or mentors familiar with your work. Ph.D. positions Funded positions will be advertised as they become available. Placement / Erasmus / Visiting students I am happy to host placement and visiting young scientists in my lab. If you are interested in joining us, please contact Dr Sisu directly.

Dr Predrag Slijepcevic Qualifications: PhD in Radiation Biology, University of Sarajevo MSc in Radiation Biology, University of Sarajevo BSc in Veterinary Medicine, University of Sarajevo Other Teaching Responsibilities:Module oo-ordinator BB3201 Genomic Medicine BB5505 Genomic & Molecular Medicine

Dr Gudrun Stenbeck Qualifications: 1993: PhD in Chemical Technology/Biochemistry, Technical University Darmstadt, Germany 1989: German equivalent of BS/MS degree in Chemical Technology, Technical University Darmstadt, Germany Other Teaching Responsibilities:Academic appointments September 2005: Brunel University London, Lecturer 2000-2005: University College London, Arthritis Research Campaign Research Fellow & Honorary Lecturer, Bone and Mineral Centre 1996-2000: University College London, Postdoctoral Research Fellow, Bone and Mineral Centre 1993-1996: Memorial Sloan-Kettering Cancer Centre, New York, USA, Postdoctoral Research Fellow, Cellular Biochemistry and Biophysics Program

Dr Barbara Tanos-Lora A global nomad, Dr Barbara Tanos received her undergraduate degree from the University Buenos Aires, Argentina, and her PhD in Molecular Cancer Biology from Duke University in North Carolina (USA). As a graduate student in the laboratory of Dr Ann Marie Pendergast, Dr Tanos became interested in how signal transduction pathways regulate basic biological processes such as the trafficking of growth factor receptors throughout the cell. During her graduate studies, Dr Tanos uncovered a novel role of Abl tyrosine kinases in the regulation of the epidermal growth factor receptor (EGFR) internalization through specific phosphorylation of a tyrosine residue and through the disruption of the EGFR/Cbl interaction. During her postdoc, Dr. Tanos began conceptualizing the idea that specific signals that drive epithelial polarity can be co- opted by cancer cells to optimize the remodeling of tumor tissue architecture, she trained with world-renowned cell biologist Dr. Enrique Rodriguez-Boulan at WCMC-NY, and wrote a review entitled “The epithelial polarity program: machineries involved and their hijacking by cancer,” and also uncovered a novel role for the scaffold protein IQGAP1 in barrier function during the establishment of epithelial polarity. After this, she began to appreciate the importance of understanding signaling from centrioles and cilia, which she hypothesized, could function as signaling hubs. Since little was known about these organelles, Barbara went to the laboratory of Dr. Bryan Tsou, an expert in the field, to learn key aspects of centrosome and cilia biology. There, Barbara identified a novel group of centriolar distal appendage proteins required for cilia formation, and uncovered the mechanism and cell cycle regulation of centriole docking to the plasma membrane. This work was published in Genes and Development, has been highly cited and it is considered to be a hallmark paper in the field. The proteins she described have now been causally linked to hereditary syndromes involving cilia defects (ciliopathies). At Brunel University, Dr Tanos’s lab focuses on understanding the mechanisms of regulation of centrioles and cilia, how they function as signalling platforms, and what the consequences of their misregulation are in disease. Using a unique mix of expertise in signal transduction, biochemistry, cancer biology and cell biology she uses this information to find and exploit therapeutic opportunities both for cancer and ciliopathies. Work from the Tanos Lab, has been recently published in Cell Reports, describing a truly novel and fascinating story on the role of primary cilia in promoting resistance to a variety of cancer drugs: and was featured in the MRC and other news websites: and Dr. Tanos was interviewed on the radio, External website: tanoslab.org

Professor Michael Themis Dr Themis is a Reader in the Department of Life Sciences Brunel University London and an Honorary Lecturer at Imperial College, London. His research at Brunel concerns gene therapy efficacy and safety. Founding Director of TestaVec Ltd - A brunel University spin-out company Between 2015 and 2017 over 1800 gene therapy (GT) trials were initiated or approved worldwide. Large pharmaceutical companies including GSK, Novartis, Astra Zeneca and Pfizer are investing heavily in gene therapy virus technology and two new licensed products, ‘Glybera” (Uniqure) and Strimvelis (GSK) have now entered the market. Treatments for several genetic disorders are available including cancer, however, no standardised platform has been available to test safety, which is concerning following the development of leukaemia in several children treated for X-linked immunodeficiency by this therapy. Dr Themis has recently launched the first company that focusses on screening the safety of gene therapy. The technology developed and led by Dr Themis in collaboration with UCL, KCL, GeneWerk, Germany, the National Institute for Biological Standards and Control and NMI, Germany, won the SBRI InMutaGene CRACK-IT Challenge. This work, which was funded by the NC3Rs and sponsored by GSK and Novartis has generated the first human induced pluripotent stem cell (iPSc) based platform that evaluates the safety of gene therapy products. The intension is to use this technology prior to patient exposure as a pre-screening service that identifies patient tolerance to gene therapy and to profile vector side effects next to established reference standards. With IP filed, TestaVec Ltd, which is a spin-out of Brunel University will support academics and industry alike to enter their products safety into the clinic. Qualifications: BSc: 1st class honours with Brunel University London and University Prize PhD: 1994 entitled “Insertional mutagenesis:experiences at the hprt locus” Post Graduate Certificate in Learning and Teaching in Higher Education (PGCert) Post Graduate Certificate in Intellectual Property Law (PGCert) Training Persuasion and Assertiveness - 2008 PgCert in Teaching - 2008 PgCert in Patent Law - 2010 Blackboard Learn - 2012 Biological Monitoring for Health and safety – HSE Buxton 2012 Introduction to the Principles and Practices of working at Containment Level 3 – HPA Porton Down 2013 Research Focus (h-index 34, Google Scholar) His research expertise covers gene therapy and its related genotoxicity to the genome, stem cell biology and cancer. His team is currently funded on projects related to gene therapy vectors and their side effects on the host. His expertise in adenovirus, retrovirus and lentivirus gene therapy vectors biology enables his research to be world class. He recently won the SBRI Innovate UK, NC3Rs InMutaGene CRACK-IT Challenge Phase I and with GeneWerk, Germany, won the Phase II award to develop a novel platform to assess the genotoxic risk of LV and AAV vectors using a human induced pluripotent stem cell platform. This work is also supported by GSK. His group is currently reprogramming these cells to numerous cell types representing organs that are intended for gene therapy. This model will ultimately make available genotoxicity testing in a personalised manner. His research is also concerned with gene therapy of several genetic diseases including Cystic fibrosis, Duchenne muscular dystrophy, familial hypercholesterolaemia, haemophilia B and Freidriech ataxia (FRDA) for which mouse models exist. He also holds Ataxia UK award for his FRDA gene therapy research. He has over 66 peer reviewed publications in gene therapy periodicals. He collaborates world wide with leaders in the field of gene therapy Research awards: Wellcome Trust, MRC, SPARKS, Muscular Dystrophy Association, Brunel BRIEF Award, Ataxia UK/FARA Australasia and US and MRC NC3Rs/Innovate UK, GSK, N4Pharma and ICure Patents A Suspension Culture Cell Line Capable of Producing Retrovirus Particles Combinations and methods for promoting in vivo cell proliferation and enhancing in vivo liver-directed gene transductions Transgenic organism (Oxford BioMedica) A fetal and neonatal model for vector safety and design. P38561GB/TF Method of testing a gene therapy vector’ UK Patent Application GB 2564437 A. PCT/GB2018/051937 Method of predicting the likelihood of success of gene therapy’ PCT/GB2017/05288. EU IP 17797413.6 Major presentations The 23rd Annual Meeting of The American Society for Gene and Cell Therapy, Virtual. USA, 2020 NC3Rs Case Study presentations July 2019 (Invited speaker) Swiss Toxicology Society, Switzerland, Nov 2018 (Invited speaker) Hammersmith poster for business Oct 2018 NC3Rs London, Cancer Gene Therapy Workshop, Nov 2018 (Invited speaker) Novartis, Basel, 2018 SEHTA, Brunel University, Oct 2018 (Invited speaker) GSK research meeting, Stevenage Nov 2018 (Invited speaker) British Society of Gene and Cell Therapy 2018 (Invited speaker) Ataxia UK, Pisa, Italy 2017 British Society of Gene and Cell Therapy 2017 (Invited speaker) Ataxia UK, Windsor 2015 (Invited Speaker) Genethon, Evry, Paris 2013 (Invited Speaker) Clinigene, Luca, Italy 11th 2009 (Invited Speaker) FARA, Ataxia UK 2012, University of Pennsylvania, USA (Invited speaker) Gene Therapy workshop, Jerusalem, Israel 2010 (Invited Speaker) RAHMS, Paphos, Cyprus 2008 (Invited Speaker) RAHMS Paphos, Cyprus 2010 (Invited Speaker) Royal Veterinary College, Potter’s Bar, Hatfield, 2009 (Invited Speaker) The 3rd Stem Cell and Clonality and Genotoxicity Retreat, Orlando, Florida. USA, 2006 (Invited speaker) Clinigene during the 14th Annual Meeting of the ESGT Athens, Greece, 2006 (Invited speaker) The 9th Annual Meeting of The American Society for Gene Therapy, Baltimore. USA, 2005 (Invited speaker) The 13th Annual Meeting of the ESGT Prague, Czech Republic, 2005 (Invited speaker) The 3rd Annual Workshop “Viral Vectors” of the Gesellsschaft fur Virologie (GFV) and 12th Annulal Meeting of the German Society of Gene Therapy, Germany (2005), (Invited speaker) The 8th Annual Meeting of The American Society for Gene Therapy, St. Louis. USA, 2005 (Invited speaker) The 2nd Annual Meeting of The British Society of Gene Therapy, 2005. ‘A potential in vivo model to test for the safety of lentivirus gene therapy vectors’ (Invited speaker) The 7th Annual Meeting of The American Society for Gene Therapy, Minneapolis. USA, 2004 (Invited speaker) The 11th Annual Meeting of the ESGT Edinburgh, Scotland, 2003 (Invited speaker) The 6th Annual Meeting of The Society for Gene Therapy, Washington. USA, 2003 (Invited speaker) The 10th Annual Meeting of the ESGT Antibes, France, 2002 (Invited speaker) The 5th Annual Meeting of The Society for Gene Therapy, Boston. USA, 2002 (Chosen speaker) The 29th British Congress of Obstetrics and Gynaecology, Birmingham, Great Britain, 2001 (Invited speaker). The 4th Annual Meeting of The Society for Gene Therapy Seattle, USA, 2001. The 9th Annual Meeting of the ESGT Antalya, Turkey, 2001 (Invited speaker) The 8th Annual Meeting of the ESGT Stockholm, Sweden, 2000 Editorial Boards Journal of Virology and retro virology Liver Research – Open Journal Hindawi Publishing Corporation Clinical HIV/AIDs research Editorial board Bentham Science Heighpub Journal of Clinical Virology Journal of Hematology and Diabetes Journal of Hematology and Oncology Forecast www.scienceforecastoa.com Gene therapy and related genotoxicity Teaching Responsibilities: Module co-ordinator of level 3 'Genomic Technologies' Level 2 lecturer of 'Genomic Technologies' Other Teaching Responsibilities:Position history 2006 - present: Lecturer Brunel University London, Uxbridge (HFCE funded) 2006 - present: Honorary Lecturer Imperial College London 2005 - 2006: Research Lecturer, Imperial College London. MRC, Wellcome Trust Value In People Award (Welcome Trust and HFCE funded) 2000 - 2005: Research Lecturer, Imperial College London (MRC funded) 1998 -1999: Senior post-doctoral Research Fellow, Imperial College (MRC funded) 1994-1998: Post-doctoral position, St. Mary's Hospital, Paddington, London (March of Dimes funded)

Dr Kazunori Tomita Research theme: Telomere biology and chromosome maintenance Career: 2019- Senior Lecturer in Biomedical Sciences, Department of Life Sciences 2018- Honorary Senior Research Associate, UCL Cancer Institute, University College London, UK 2010-2018 Principal Research Fellow, UCL Cancer Institute, University College London, UK 2010-2016 Cancer Research UK Career Development Fellow 2010 Postdoctoral research fellow, Department of Hematology, Imperial College London, UK 2004-2009 Postdoctoral research fellow, Cancer Research UK, London Research Institute, UK 2001-2004 Ph. D. in Environmental Sciences, Shizuoka University, Japan Chromosome maintenance Why can cancer cells propagate indefinitely? A clue can be found at chromosome ends, the telomeres. Telomeres are indispensable for chromosome stability in propagating cells, and the length of the telomeres defines the number of times a cell can divide. Elucidating the homeostatic systems and functions of telomeres are therefore essential for understanding cancer cell immortality as well as cellular ageing. Our cells harbour all the information required for the construction of our body and life cycle. These data are ‘encoded’ by long linear DNA molecules, called chromosomes. The physical end-regions of the chromosome, called telomeres, play critical roles in the maintenance of chromosomes.Stresses from both outside and inside cells can cause breaks in chromosomes, but these broken DNA sites are usually mended by DNA damage surveillance and repair systems. Although chromosome ends harbour a similar structure to the DNA ends at break sites, telomeres protect against these surveillance systems to avoid inappropriate repair, which if left un-checked, would cause end-to-end fusions of the chromosomes. Despite the essential function of telomeres in chromosome maintenance, chromosomes lose telomeric DNA progressively with each round of cell division. In order to protect the chromosomes, shortened telomeres elicit a checkpoint dependent arrest of cell propagation, resulting in cellular ageing (senescence) [Fig. 1]. Figure 1 - Model of telomere shortening and the checkpoint - Telomeres (green bars) shorten progressively with cell divisions. Shortened telomeres are recognized by checkpoint machinery, and induce cellular senescence. However, if telomerase is expressed, telomeres are replenished, allowing further cell divisions. Cancer cells escape this programmed cell scenesence by activating a protein called telomerase. Telomerase counteracts the DNA loss at short telomeres by replenishing telomeric DNA. Using this protein, cancer cells are able to maintain chromosome ends, and therefore continue dividing [Fig. 1]. However, cancer cells somehow maintain short telomeres compared to normal cells. Such short telomeres or unprogrammed telomere maintenance can lead to uneven chromosome segregation, which causes malignant progression. We can recapture this issue in fission yeast model [Fig. 2]. Figure 2 - Telomeres and chromosome segregation - A series of frames taken from films of live yeast undergoing chromosome segregation. Time progresses towards the right. Chromosomes are shown in cyan. Red dots (spindle pole body) represent the marker for chromosome segregation. Chromosomes condense and migrate towards the poles in the control. In the ccq1 mutant cell, chromosomes stretch between the two poles, presumably caused by chromosome end-to-end fusions or entanglements [shown in arrow]. Projects: We aim to understand how telomeres are maintained and how they act to guide chromosomes through cell divisions. To address these issues, we primarily employ fission yeast as a model system. Fission yeast telomeres have a similar structure and function to human telomeres and are also maintained by telomerase. This model organism allows an intricate genetic approach to be used to unravel mechanisms at the molecular level. Studies from fission yeast will greatly contribute to the understanding of telomerase action in normal and cancer cells in humans (Armstrong & Tomita 2018 review). We hope this will lead to the development of advanced cancer treatments and techniques to aid with diagnosis. We are interested in the alterations in telomere components and structure that occur during the cell cycle or telomere erosion. This telomere plasticity may contribute to multiple functions of telomeres in various conditions. The following aims are currently being investigated. 1. Molecular mechanisms underlying telomerase actionTo extend telomeric DNA, telomerase (Trt1-TER1-Est1) first needs to contact the telomere complex [Fig. 3]. This recruitment process itself dose not engage telomerase activity, rather it promotes an alternative interaction between the telomere proteins and telomerase. Ccq1 was found to be a telomerase recruiter that connects the main telomere protection proteins, Pot1 and Tpz1, with telomerase (Tomita & Cooper 2008). After recruitment, Tpz1 seems to interact directly with telomerase to control its activity (Armstrong et al. 2014). Reassembly of the Tpz1-Ccq1 complex with telomerase is crucial for telomere maintenance. We found that fission yeast Tpz1 is functionally and structurally well recapturing hTPP1/ACD, a human counter part (Hemanth and Collopy et al. 2018). Ccq1 also interacts with the chromatin remodeling complex, SHREC, and this complex acts as negative regulator of telomerase to counter-act retention of telomerase at the telomere (Armstrong, Moiseeva et al. 2018). We are investigating the molecular links between the telomeric proteins and telomerase components, and exploring how these connections are regulated. Figure 3 - Model for telomerase interaction and activation - Dynamic interactions of the telomeric protein complex (Pot1-Tpz1-Ccq1) with telomerase (Trt1-TER1-Est1).1) A telomere with marked Ccq1 becomes a target of the telomerase subunit Est1. 2) Interaction of Est1 with Ccq1 releases Ccq1 and Est1 from the telomere and telomerase, respectively. 3) Interaction of Tpz1 with telomerase and re-association of Ccq1 are required for telomere maintenance.4) SHREC-bound Ccq1 promotes release of telomerase from the telomere 2. Regulation of telomerase activity at telomeres and telomere length homeostasis - The extent of telomere lengthening is controlled via a number of processes including the expression level and assembly of telomerase, accessibility of telomerase to telomeres and telomerase processivity. dysfunction in any of these process resulted in bone with short telomere, leading to telomeropathy (or short telomere syndrome). This is degenerative disease, causing progressive tissue defects including bone marrow failure and fibrosis. Identification of new genes involved in these process is needed to support genetic diagnostic of these patients. we identified an RNA chaperon Lar7 as a telomerase assembly factor in fission yeast (Collopy et al. 2018). We hope our findting will support our understanding of human telomerase assembly. Telomerase is not expressed in most mammalian somatic cells. However, mild expression of telomerase, as seen in some pluripotent stem cells, can delay telomere shortening. Reproductive germ cells and unicellular organisms highly express telomerase, enabling telomeres to be maintenaned at a certain length (telomere length homeostasis). Since many cancer cells cannot maintain long telomeres despite highly active telomerase, we predict that telomerase regulation at the telomere is altered in these cells. 3. Telomere function and regulation in meiotic prophase - Telomeres function not only in maintaining intact chromosome ends but are also directly involved in meiotic progression. Organisms diversify and propagate their genetic information throughout successive generations through the process of meiosis. Understanding the process of meiosis is important, as meiotic defects are a major reason for miscarriage in humans. During early meiotic prophase, telomeres gather near the microtubule organizing-center (MTOC) to form the so-called ‘bouquet’ structure [Fig. 4]. Failure to form the chromosomal bouquet results in aberrant spindle pole formation and meiotic spindle defects in fission yeast (Tomita & Cooper 2007). The telomeric proteins accumulate modifications as meiotic prophase progresses (Amelina et al. 2015), and completion of meiotic recombination triggers termination of the bouquet stage, which in turn promotes accumulation of the cyclin dependent kinase for prophase exit and formation of functional spindle (Moiseeva et al. 2017). Currently, we are investigating what telomeres monitor during meiotic prophase and how telomeres signal to the meiotic spindle. Intriguingly, some cancer cells can utilize meiotic telomeres to maintain chromosome ends. Thus, we aim to understand the structural and functional changes occurring at telomeres throughout meiotic progression, permitting a greater understanding of a central function of telomeres. Figure 4. Chromosomal BouquetAll chromosome ends move to near the MTOC (red). The resulting chromosomal structure resembles a bunch of flowers. The bouquet has been observed in diverse organisms including yeast and human. Key words of research interests: Molecular biology, cancer biology, RNA biology, transcriptional regulation, cellular senescence, genetic and protein-functional diversity between species, telomere-associated diseases and disorders Telomeres and telomerase, chromosome biology, DNA damage responses, the cell cycle, meiosis

Dr Sabrina Tosi Dr Sabrina Tosi graduated in Biological Sciences at the University of Milan (Italy) in 1989 and then attained her post-graduate degree in Human Cytogenetics at the University of Pavia (Italy) in 1992. Between 1989 and 1993 she was a research scientist at the Department of Paediatric Haematology, University of Milan, Ospedale San Gerardo, Monza (Italy). During this time she worked also as a visiting research scientist at Oncogenetic Laboratory, Children's Hospital, University of Giessen (Germany) for approximately a year. In 1994, Dr Tosi transferred to the University of Oxford to work as a research scientist, she then enrolled and completed her DPhil studies in 1999. She continued to work at the University of Oxford until July 2005, when she was appointed as Lecturer in Biosciences at Brunel University London. Dr Sabrina Tosi is the Head of the Leukaemia and Chromosome Research Laboratory. Her research focuses on the contribution of chromosomal abnormalities to leukaemia. Dr Tosi has a particular interest towards the study of childhood leukaemia. This interest dates back to 1989, when she started her scientific career soon after her undergraduate studies. The main methodological approach used in the laboratory involves the application of modern molecular cytogenetic techniques to unravel the genetic changes at the basis of leukaemic transformation. The projects currently ongoing in the lab are based on the use of fluorescence in situ hybridisation (FISH), immunofluorescence and microscopy. These methods have enabled the characterization of new non-random chromosomal translocations specifically associated with certain leukaemia subtypes. Dr Tosi’s research interests extend to view chromosomal alterations in context with the higher order chromatin organisation and expression patterns. Teaching Responsibilities: Module and programme teaching responsibilities FHEQ Level 4 “Career Planning and Innovation” study block co-ordinator

Dr David Tree Qualifications: BSc, Genetics, The University of York, UK, 1996 Ph.D, The University of Cambridge, UK, 1999 PG-Cert Higher Education, Brunel, 2008 Fellow of the Higher Education Academy, 2016 Senior Fellow of Advance HE, 2019 Our group seeks to understand how cells within tissues integrate intra- and extra-cellular signals to regulate polarity, growth and homeostasis after cell death in young and old organisms. We use Drosophila genetics to study the biology of a well-understood population of stem cells in the fly testis. Adult stem cells maintain tissues by replenishing lost or dying cells to ensure the integrity of the organism. All cells within an organism, including stem cells, can be challenged by cellular stresses that lead to cell death. How they respond to damage-induced apoptosis by dividing to maintain the number of cells necessary for the homeostasis of a tissue is a process known as Apoptosis Induced Proliferation (AIP). In both normal development and adult life after damage it is vital that cell populations reach the correct size, to maintain their function, but that they do not over-grow, which can lead to cancer. We are interested in how AIP functions in the stem cells of the fly testis and how they respond to damage to ensure the stem cell population is not depleted but also that it does not over grow. Drosophila genetics Planar Cell Polarity (PCP) signalling Stem cells Apoptosis induced proliferation Hutchinson-Gilford Progeria Syndrome Teaching Responsibilities: LS1700 Teamwork and Presentation BB2709 Genetics, Genomics and Human Health BB5709 Cell Signalling in Health and Disease Academic Appointments 2005 - Brunel University London November 1999 – August 2005 – Post-Doctoral Researcher , Stanford University

Professor Paola Vagnarelli Qualifications: PhD in Genetics and Molecular Biology, University of Pavia, Italy Degree in Biological Sciences, University of Pavia, Italy Professional experience 1993-1996 Postdoctoral Research Fellow, Dipartimento di Genetica e Microbiologia Universita’ di Pavia 1997 Visiting Scientist MRC Human Genetics Unit, Edinburgh 1998- 2012 Postdoctoral Research Fellow Wellcome Trust Centre for Cell Biology Edinburgh (Prof WC Earnshaw) 2102 Lecturer School of Health Sciences and Social Care, Department of Biosciences, Brunel University London Cell division Chromatin Epigenetics Cancer We are interested in studying cell division and in partiular the dynamics and organisation of chromatin duting the transition from mitosis to G1. Teaching Responsibilities:PI Chromosome structure and dynamics laboratory