institute of molecular cancer research msc ...40eb010a-7723-401c-b6b3-07ea… · msc/diploma...
TRANSCRIPT
Molecular characterization of new Homologous Recombination factors during DNA replication stress
Growing evidence suggests that replicative stress-induced genomic
instability underlies the cancer predisposition in individuals with sporadic
or hereditary mutations in specific Homologous Recombination (HR) and Fanconi Anemia (FA) genes, besides their well-established role in Double-Strand Break (DSB) and interstrand-
crosslink (ICL) repair.
The student will join a group of 10 researchers and – under the direct
supervision of a postdoc - will focus on investigating the molecular role in
replication stress of new HR factors, recently identified by a high-content microscopy-based genetic screen.
The student will learn and performindependently a number of different approaches, ranging from standard
molecular and cell biology methods tomore specialized techniques such as
Quantitative Imaging-based Microscopy(QIBC), in vivo DNA labelling and
chromosome spreading, and ElectronMicroscopy of replication intermediates.
Institute of Molecular Cancer Research
24h Cdc25A
Application: [email protected] brief motivation letter + CV
Starting date: September 2016
Duration: 12 months
www.imcr.uzh.ch
MSc/Diploma positionDNA Replication and Genome Instability Group
Prof. Massimo Lopes
Matthias Altmeyer, PhD Department of Molecular Mechanisms of Disease University of Zurich Winterthurerstrasse 190 8057 Zurich
E-Mail: [email protected] Phone: + 41 44 63 55 475
Master Student Position in Genome Instability Research Irchel Campus - University of Zurich
We are looking for a talented and highly motivated MSc student to join our research group. Starting date: Negotiable. Work Description: Research in our group aims at elucidating the mechanisms that proliferating cells use to protect their genome from attrition and instability. In addition to molecular and biochemical approaches, we combine automated quantitative microscopy of cell populations with targeted perturbations of cell functions through chemical and reverse genetics to identify factors involved in genome integrity maintenance and characterize their molecular functions. Qualifications: You should have a strong interest in molecular cancer research, a high level of motivation, and feel comfortable and self-confident when working in the lab. Prior experience with mammalian cell culture and standard molecular biology techniques is of advantage. Good communication skills and enthusiasm will allow you to productively interact with our international research team. Work environment: We offer excellent supervision in a young and dynamic research group, comprehensive scientific education, and easy access to state-of-the-art technologies including advanced fluorescence microscopy. Applications: For more information about our research group and ongoing projects please visit our webpage or contact us directly. Interested candidates should send their CV together with a short motivation letter to [email protected].
March 2016
Master Thesis Project: Inflammatory microenvironment during metastasis
Metastasis is the primary cause of cancer-‐related mortality. Tumor microenvironment is composed of leukocytes and stromal cells that significantly affect cancer progression. Chemokines are the key cytokines, which promote the recruitment and the polarization of leukocytes. Our projects aim to understand the function of particular chemokine-‐chemokine receptors pairs using in vitro techniques (e.g. co-‐culture assays) and validate their role in vivo.
Students will perform the following techniques: cell culture, IF microscopy, flow cytometry, animal experiments, q-‐PCR, Western blot etc.
Supervisor: Prof. Dr. Lubor Borsig
Institute: Institute of Physiology
Contact: e-‐mail: [email protected], Phone: 044 635 5134
Link: http://www.physiol.uzh.ch/en/research/institutegroups/grborsig.html
Topic Role of tumor suppressor variants in response to chemotherapy in mesothelioma
Short description
BRCA-1 associated protein 1 (BAP1) is mutated in 25% of mesothelioma patients. Loss of function of BAP1 is associated with changes in histones ubiquitination and alteration of DNA damage response. In tumors with no genetic alterations, splice variants which may lead to loss of function, have been observed. Our aim is to better characterize the role of their expression in sensitivity to drugs combinations targeting genomic instability. We are analyzing the sensitivity of mesothelioma cells expressing different levels of BAP1 variants and grown as spheroids toward PARP inhibition in the presence or absence of drugs decreasing the expression of DNA repair enzymes. Mechanism underlying differential sensitivity, including histones ubiquitination will be investigated. The candidate master student will have the opportunity to learn cell biology techniques such as 2D and 3D cell culture, drug treatment, viability assessment assay, Western blots, immunofluorescence.
Supervisor Institute E-mail Phone
Agata Okonska, PhD student, Dr. Rossella Parrotta, PD Dr. Emanuela Felley-Bosco, Laboratory of Molecular Oncology Sternwartstrasse 14, 8091 Zurich 044 255 2771
Conditions Start: Spring 2016 Links http://www.zkf.uzh.ch/de/ResearchGroups/Stahel.html
Spring 2016 Maries van den Broek
Masterprojects Maries van den Broek (Institute of Experimental Immunology) Contact: 044-6353722, [email protected] Our group studies the interaction between cancer and the immune system. There is no doubt that the immune system recognises and can control cancer cells but this so-called immune surveillance failed in clinically apparent cancer. The reasons for this failure can be manifold and include loss of determinants that are targeted by the immune system and the creation of an immune-hostile microenvironment. Clinical observations and questions are the inspiration for our research projects, but we address such questions often using model systems and a fundamental approach. We subsequently validate our results using material from cancer patients. Specifically, Master Students can participate in following projects: (i) Immune control of metastasis formation and/or outgrowth (ii) Radiotherapy-induced stimulation of tumour-specific immunity (iii) The role of tertiairy lymphoid structures in cancer (iv) Wnt/β-catenin signalling in non-melanoma skin cancer In the context of a Master thesis, students will become proficient in following techniques: Cell culture, animal experiments, immunofluorescence and -histochemistry, flowcytometry, cell sorting, quantitative real-time PCR, western blotting, immunological assays
Identification of the AML and CHD1L (oncogene)-‐specific cellular ADP-‐ribosylome
Supervisor: Prof. Dr. Dr. Michael O. Hottiger Institute: Department of Molecular Mechanisms of Disease (DMMD) E-‐mail: [email protected] Phone: 044 645 5474 Conditions: Start immediately Links: http://www.dmmd.uzh.ch/en/research/hottiger.html
Master Thesis Project Master of Science in Biology
Intracellular ADP-‐ribosylation (ADPr) is a phylogenetically ancient, covalent, and reversible post-‐translational protein modification (PTM) catalyzed by ADP-‐ribosyltransferases that are structurally similar to diphtheria toxin (ARTDs, formerly PARPs), and requires nicotinamide adenine dinucleotide (NAD+) as a substrate. Protein modifications can either be mono-‐ or poly-‐ ADPr and have been implicated in cancer, as inhibition of these enzymes by so-‐called PARP inhibitors is anti-‐tumorigenic in both experimental and clinical studies. The identity of the ADP-‐ribosylated proteins modified by ARTDs has been extensively debated, and different amino acids have been put forward as ADPr acceptors. This knowledge is important for the development of more specific ADPr inhibitors.
Our research over the past few years has led to the establishment of mass-‐spectrometry based screening platform for the identification of ADP-‐ribosylated peptides.
In this project, we aim to identify in a comprehensive way 1) all proteins ADP-‐riboslated in the Kazumi cell line (acute myeloid leukemia), whose proliferation is dependent on ADPr and 2) particularly the modified proteins interacting with the macrodomain of the oncogene CHD1L (chromodomain helicase/ATPase DNA binding protein 1-‐like gene). These findings should help to obtain further insights for a possible treatment of tumors with PARP inhibitors.
Department of Molecular Mechanisms of Disease
Master’s thesis Project 1 Topic: Determining cellular and micro-environmental impact on MAPK activation in medulloblastoma using FRET probes Our laboratory investigates the pediatric brain tumor Medulloblastoma (MB) at the molecular and cellular levels. We identify novel potential therapy targets that could be blocked to prevent metastatic dissemination of MB in the brain. We have established microscopy image-based screening approaches to identify novel drug targets acting in growth factor signaling pathways that promote migration and invasion of the tumor cells. Among those are the Extracellular Regulated Kinase ERK and the c-jun N-terminal Kinase JNK, which are required for growth factor-induced MB tumor cell migration and invasion. To determine whether ERK and JNK are active in migrating and invading tumor cells, the Master’s student will establish the expression of Förster Resonance Energy Transfer (FRET) probes for ERK and JNK in MB cells. He or she will then monitor ERK and JNK activation in response to growth factor stimulation and in MB cells infiltrating into the cerebellar tissue, to determine cellular and micro environmental impact on MAPK activation in MB. The aims of the present Master Thesis project are:
1. To establish transient and stable expression of FRET probes for ERK and JNK in MB cells
2. To validate FRET probes in growth factor stimulated and migrating MB cells 3. To monitor ERK and JNK activation in MB cells during collagen matrix invasion or
cerebellar tissue infiltration The Master student will develop transgenic MB cell lines and validate the functionality of the FRET sensors. He or she is expected to learn and use state-of-the art microscopy and contribute to the development of quantitative imaging to assess MAPK activation in tumor cells. Supervisors: PD Dr. Martin Baumgartner, Karthiga Santhana Kumar (Ph.D stud.) Institute: University Children’s Hospital Zürich e-Mail: [email protected] phone: 044 634 88 51 links: http://www.eicr.uzh.ch/research/oncology/neurooncology.html requirements: candidate must be enrolled in one of the following Master of Science in Biology Programs of the University of Zürich: Human Biology, Cancer Biology, Molecular and Cellular Biology starting date: immediately
Master thesis Project 2 Topic: Proliferate or migrate – Does crosstalk between the Hippo pathway and growth factor signaling maintain proliferation-migration dichotomy in medulloblastoma?
Our laboratory investigates the pediatric brain tumor Medulloblastoma (MB) to identify novel potential therapy targets to prevent growth and metastatic dissemination. In a subset of MB tumors we found the tumor suppressor Hippo pathway inactivated and causing increased expression of the YAP transcriptional activator. YAP expression in these cells promotes proliferation and restricts migration, suggesting that YAP controls proliferation positively and migration negatively. As aberrant control of proliferation and migration are key features of cancer, it is of importance to better understand YAP regulation in MB tumor cells. The subject of this Master’s thesis project is the regulation of the Hippo pathway in the context of proliferation and migration control. The student will investigate how pro-migratory signaling and anti-migratory Rho-kinase activities control Hippo pathway function and YAP-dependent expression of target genes. He or she will thus address whether dichotomy between proliferation and migration exists in MB and whether Hippo pathway function controls this process.
The aims of the present Master’s Thesis project are:
1. To determine Hippo pathway activity and function under pro- and anti-migratory conditions 2. To determine whether and how Rho kinase ROCK controls Hippo pathway activity 3. To determine whether MAP4K4 exerts dual function in proliferation-migration regulation
The Master student will use biochemical and cell biological approaches in cell-based models of SHH MB to determine pathway activity and live and fixed cell microscopy to investigate spatio-temporal control of pathway functions. Supervisors: PD Dr. Martin Baumgartner, Dimitra Tripolitsioti (Ph.D stud.) Institute: University Children’s Hospital Zürich e-Mail: [email protected] phone: 044 634 88 51 links: http://www.eicr.uzh.ch/research/oncology/neurooncology.html requirements: candidate must be enrolled in one of the following Master of Science in Biology Programs of the University of Zürich: Human Biology, Cancer Biology, Molecular and Cellular Biology starting date: immediately
DNA DAMAGE RESPONSE AND GENOME INSTABILITY To preserve genomic integrity cells evolved a complex process called “DNA damage response” or DDR, responsible for the detection and repair of DNA lesions. Phosphorylation and ubiquitination are master regulators of DDR; alteration of these processes leads to genomic instability, which is one of the most pervasive characteristics of human cancers. We identified a crucial player of this pathway, namely the ubiquitin ligase RNF168, and we characterized a novel ubiquitin-based code – made by K27 non-canonical ubiquitination targeting the K13/K15 site on histone H2A - that cells use to mark chromatin structure, to signal DNA damage and to activate DNA repair.
Recently we performed quantitative mass spectrometry (SILAC) to identify novel DDR factors. Among few potentially interesting candidates, we found a deubiquitinating enzyme (DUB) associating with RNF168. We started characterizing this DUB and we already obtained intriguing results, confirming its essential role in the activation of the DDR pathway. The proposed project aims at further understanding the mechanism of action of this DUB in the context of chromatin modification and DDR, and how this will impact on the maintenance of genome integrity. The student will be part of the lab, dealing with different aspects of the project and with various techniques: biochemistry, molecular and cellular biology, proteomics, FACS analysis, immunofluorescence and imaging technology.
Institute of Molecular
Cancer Research
Lorenza Penengo Group www.imcr.uzh.ch/research/Penengo.html
Application: [email protected] Starting date: Spring 2016 Duration: 12 months
MSc Thesis Position in Cancer Biology
Master Thesis Project Project Title: JNK signalling in bile duct development and tumor formation in the liver
Background / project description: The Weber group at the Institute of Surgical Pathology, University (UZH) and University Hospital (USZ) Zurich, has a focus on liver and intestinal inflammation and carcinogenesis. Research projects involve mouse models of diseases as well as analyses of human tissues. In addition to basic research projects, the group works on projects arising from routine diagnostic clinical and molecular pathology (see e.g. Wolf et al. (2014) Cancer Cell; Protzer et al., (2015) Modern Pathology; Friemel et al. (2015) Clinical Cancer Research). The project offered is dedicated to studying the role of JNK signalling in bile duct development and tumor formation in the liver. The work comprises mostly analyses of genetically modified mice, but also of human liver tissues.
What the student learns: In the context of her/his Master thesis, the student has the opportunity / is expected to become proficient in following techniques: animal experiments, biochemistry and molecular biology (DNA and RNA preparation and analyses including e.g. quantitative real-time PCR, siRNA-mediated depletion, western blotting, immunological assays), and morphological analyses (including histology, immunohisto-chemistry; light and immunofluorescence microscopy).
Requirements: The student is expected to become a part of our research group. High motivation and dedication are essential. Interested candidates are invited to send a CV and transcript of records.
Contact: Supervisors: Marc E. Healy, Ph.D., Achim Weber, M.D. Institute: Institute of Surgical Pathology, UniversitätsSpital Zürich e-mail: [email protected]; [email protected] links: http://www.klinische-pathologie.usz.ch/forschung/weber-lab/Seiten/research-group-members.aspx
Master Thesis Project!Master of Science in Biology!
DNA Repair in Mitosis!Among the most toxic DNA lesions are DNA double-strand breaks (DSBs). Since both of the DNA strands are affected, these lesions can easily result in the loss of genetic information should the DNA ends dissociate before the successful completion of DNA repair. It has been shown that the repair of DSBs is suppressed in mitosis to avoid telomeric fusions of sister chromatids. Thus, cells must ensure that the broken DNA ends are kept together throughout mitosis to avoid loss of entire chromosome fragments during cell division. In this project we are studying proteins that accumulate at sites of DSBs on mitotic chromosomes and may be implicated in tethering unrepaired DSBs. Supervisor: PD Dr. sc. nat. Manuel Stucki Institute: Dept. of Gynecology, USZ E-mail: [email protected] Phone: 044 556 30 40