ICA Speaker: Prof. Josef Thalhamer, PhD.
University of Salzburg, Department of Molecular Biology
Hellbrunnerstr. 34, A-5020 Salzburg, Austria
ICA Secretary: Elisabeth Eppacher
Fax: +43-(0)662-8044-5751, Email: elisabeth.eppacher@sbg.ac.at
INTERNATIONAL PhD PROGRAM
Immunity in Cancer and Allergy – ICA
APPLICATION FORM
Surname:
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1
Education
University / Polytechnic College:
Dates (from - to):
Honours degrees:
Awarded:
Anticipated:
Field of study:
If you have already obtained your degree, please scan the certificate and send a pdf-file.
Note: only diplomas and degrees equivalent to an Austrian Master's degree are acceptable.
Among these are German diplomas as well as Master's and Bachelor's Honours degrees
which include project work summarized in a written thesis (certain British or equivalent B. Sc.
Honours projects may also be acceptable).
Candidates who have not yet obtained their degree will be accepted if they can make
plausible that they will finish their studies within the next 6 months.
If you have already obtained a degree, please briefly specify in the space below the
occupation(s) you have pursued in the interim.
Additional Education (if applicable)
List additional Universities/colleges where you have earned a degree
2
Education and training (table)
Give a summary in tabular form of your education and training at the university, college, etc.
(please do not exceed one page).
3
Coursework:
Please list the courses you have taken and the grades obtained. Include all university level or
other relevant courses. If you have passed final university examinations, please provide
details (do not exceed one page).
4
Research/technical laboratory experience:
If you have any research experience, please list the techniques/methods you have learned
and describe the nature of the project and your contribution (please do not exceed one
page.)
5
List of Publications/Abstracts/Presentation at Meetings (if applicable)
6
Scientific interests
Write a short essay about the area of research (within the scope of the ICA program) that you
find most interesting (please do not exceed 300 words).
Preferred research topics / research groups
In the Appendix of this application form (page 12) you find a short description of the thesis
projects available.
You have to select 2 thesis projects (briefly justify your choice).
Your first choice:
Your second choice:
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Honours, scholarships, prizes and awards
Please list any honours or awards that you feel relevant to this application. Include dates and
a short description.
Outside interests, hobbies (optional)
Native and Spoken languages:
Indicate speaking, reading and writing ability (very high, high, moderate, low)
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Curriculum Vitae
(please do not exceed one page)
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References
Please list below the names and addresses of the two referees to whom you have forwarded
the recommendation form and who have agreed to write a letter of recommendation on your
behalf.
Note: The letters of recommendation are essential for your application which will not be
processed without them. It is your responsibility to ensure that the referees send their
recommendation on time.
Referee 1
First Name, Surname:
University/College, Name and Address of Institution:
Email:
Telephone Number:
Referee 2
First Name, Surname:
University/College, Name and Address of Institution:
Email:
Telephone Number:
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How did you become aware of our PhD program ?
Poster, advertisement in…., www, word of mouth recommendation,
or other (please specify)
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Appendix
ICA Thesis Projects
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Project 1 - workgroup Fritz Aberger
Topic: Hedgehog-GLI signaling controls tumor initiation, growth and metastasis of numerous
cancer entities.Targeting Hedgehog-GLI has shown striking therapeutic efficacy in some
malignancies, yet acquired and de novo resistance to small molecule pathway inhibitors pose
major challenges to the current concept of Hedgehog inhibition by blocking the essential
pathway effector Smoothened.
Cooperative signal cross-talk and non-canonical activation of oncogenic GLI transcription
factors contribute to malignant progression and can render Hedgehog-associated cancers
resistant to current therapies. Understanding the intricate signal processes and interactions
between different oncogenic drivers with the Hedgehog-GLI pathway is key to the
development of innovative, rationale-based combination treatments simultaneously targeting
interacting driver signals.
Thesis Project
“Interactions between growth factor and cytokine pathways with Hedgehog-GLI signaling”
The major aim of the project is to study synergistic interactions between selected growth
factor and cytokine pathways with Hedgehog-GLI signaling in the context of immune evasion.
The applicant will apply transcriptomics and next-generation sequencing ChIP-seq
technology to identify genes controlled by cooperative interactions of Hedgehog-GLI with
oncogenic driver signals. The study will concentrate on the functional analysis of common
target genes with a putative role in cancer-mediated immunosuppression and immune
evasion. Based on the results from these functional studies, novel combination treatments
including immunotherapy approaches will be evaluated in preclinical models of HedgehogGLI driven cancers.
Project 2 – (workgroup Albert Duschl)
Topic: Proteins readily bind to nanoparticles, due to the latter’s small size, high surface area
and depending on the particle properties, also due to steric, ionic or hydrophobic interactions.
Allergens bind to nanoparticles and it has been shown by the group that this attachment can
make allergens both more and less able to induce allergic reactions. The response depends
on the specific allergen, on the patient, and probably also on the nature of the nanoparticle.
Allergens attached to nanoparticles may thus be a risk factor for people exposed to them. On
the other hand, the possibility to load nanoparticles with allergen is an interesting option to
improve immunotherapy of allergic diseases. Both aspects shall be explored.
Thesis project
“Translational immunology of allergen-nanoparticle mixtures”
The project will investigate various recombinant major allergens both in free form and bound
to nanoparticles. It will thus determine how common the property of enhanced allergic
responses due to nanoparticle binding is and will via titration of allergen content allow to
estimate whether co-exposure under realistic conditions can lead to increased disease
states. It will also compare purified natural and recombinant allergens with allergen extracts
that are used in therapy. Preferential binding of the relevant allergens may be achieved via a
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suitable choice of nanoparticles. In immunotherapy, a strong (but anti-allergic) response of
the immune system is desired, which may be enhanced by high allergen density on the
nanoparticle surface and by sustained release from the inside of hollow particles, which can
act as a depot. Effects of free vs. NP-coupled allergens on human immune cells (dendritic
cells, monocytes, basophils) will be studied as biological readouts. The nanoparticles used
will be primarily composed of silica, which are available in house in many different forms,
including variants already tuned to therapeutic needs. Silica nanoparticles are also the most
produced nanoparticle type by weight, which implies that unintentional exposure by workers
and consumers is frequent, so additional information on their safety is welcome.
Project 3 – (workgroup Angela Risch)
Topic: Lung cancer is the most common cancer worldwide and the leading cause of cancerrelated death. The main risk factor is smoking and as a result of the exposure to carcinogens
lung tumorigenesis is driven by genetic events. However, in addition, altered epigenetic
regulation is now emerging as a key factor in tumorigenesis. Epigenetic modifications
including DNA methylation, histone modifications and deregulated miRNAs, do not change
the DNA sequence but affect the regulation of gene expression. More importantly, epigenetic
alterations are established and modulated based on environmental stimuli. Monozygotic
twins offer a unique opportunity to determine environmentally induced and disease-relevant
alterations in genome-wide methylation patterns.
Thesis project
“Inflammation-related epigenetic changes in lung carcinogenesis”
Genome-wide methylation profiles (Illumina 450K) have just been obtained for peripheral
blood cell DNA from 25 monozygotic twin pairs, suffering from the chronic inflammatory lung
disease cystic fibrosis (CF) with varying degrees of disease discordance. This unique data
set will allow identification of loci with variable methylation correlating with inflammatory
disease status. The role of genes identified in the CF twin blood methylation profile as
candidate risk genes for the development of lung cancer will be investigated utilizing existing
clinical cohorts and banked normal lung and tumor tissues. Genes will be investigated for
epigenetic, genetic and transcriptional alterations and subsequently, in vitro, by functional
studies, including methylation specific luciferase promoter assays, siRNA knockdown,
proliferation and migration assays.
Project 4 – (workgroup Josef Thalhamer)
Topic: Skin represents an important immunocompetent tissue and thus an attractive site for
vaccination. It is rich in immune cells playing a central role in initiating and shaping immune
responses. At present, several approaches are tested in preclinical and clinical studies with
the intention to implement safe and highly effective vaccination strategies.
In our lab we use the P.L.E.A.S.E. vaccination platform, which can circumvent the stratum
corneum in a highly reproducible, but also adaptable manner by introducing aqueous
micropores via infrared laser technology. We have already demonstrated that vaccines which
specifically target dendritic cells induce potent immune responses when applied to
laserporated skin. This approach is especially promising for the design of tailor-made
vaccines with high efficacy and an optimal safety profile.
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Thesis project
“Development of a modular nanoparticle vaccine platform for skin vaccination”
The aim of this thesis project is to develop a next generation nanoparticle vaccine platform,
which includes defined particles size, specific targeting of immune cells and activation of
different immunostimulatory pathways. In collaboration with the Department of Material
Sciences, we will create a modular system using azido-functionalized silica nanoparticles to
which any molecule of interest can be coupled and functionalized via alkyne-azido click
chemistry. This system will enable to generate tailor-made vaccines which can induce
different immune polarizations (Treg, TH1, TH2, TH17) based on the modular components
used. State-of-the-art mouse models and immunological technology/methods will be used to
investigate the vaccines and the cellular and molecular mechanisms underlying immune
polarization.
Project 5 – (workgroup Silja Wessler)
Topic: The human pathogen Helicobacter pylori is a class-I carcinogen that is strongly
associated with the induction and progression of chronic gastritis, ulceration, gastric cancer
and MALT (mucosa-associated lymphoid tissue) lymphoma in the human stomach. MALT
lymphoma originates from B cells in the marginal zone of the MALT, but the knowledge of H.
pylori-deregulated signaling in B cells is low. However, functional interaction of bacterial
effectors with the complex network of host signal transduction pathways is the crucial step in
pathogenesis. In this project, we will analyze the regulation and functional consequences of
non-receptor tyrosine kinases in H. pylori-infected B cells.
Thesis project
“Helicobacter pylori-deregulated signal transduction in MALT lymphoma”
The project focuses on the investigation of the molecular mechanisms how H. pylori factors
and translocated effectors interfere with B cell functions. In a first part of the project, we will
analyze the non-receptor tyrosine kinases of the Src and Abl families, which represent
druggable signaling molecules in patients. In a second approach, a detailed screening of
phospho-proteins and regulated kinases will be performed and compared with epithelial cells.
Attractive candidate targets will be examined for their implication in B cell activation,
proliferation or apoptosis.
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