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PhD Scholarships

4 Year CRUK PhD Studentship – September 2018 Hypoxia-induced Genetic Instability in Prostate Cancer

*4 Year CRUK PhD Studentship – September 2018*
_*“Hypoxia-induced Genetic Instability in Prostate Cancer”*_

*Translational Oncogenomics Research Group – Professor Robert Bristow*

Control of genome stability requires careful coordination between cell cycle checkpoint control and DNA repair mechanisms. Defects in the repair of DNA double-stranded breaks have been associated with acquiring genetic instability; particularly in genes responsible for homologous recombination (HR) such as BRCA1 and BRCA2. Defects in these genes lead to an increased risk of ovarian and breast cancer in women and prostate cancer in men. BRCA2- associated prostate cancers have a particular poor outcome with more than 50% of men dead at 5 years after local therapy. More recently, other DNA repair gene mutations or dysfunction have been linked to aggressive prostate cancer leading to castrate resistance and the metastatic phenotype.

All solid tumours, including prostate cancer, contain sub-regions of dynamic changes in nutrient and oxygen metabolism. Hypoxia (low oxygen tension) leads to a number of aggressive tumour cell phenotypes and genetic instability, in part, driven by the down regulation of gene expression and translation of HR genes (Bristow and Hill, Nat Rev Can, 2005). This can drive a microenvironment-induced “BRCAness” leading to a contextual synthetic lethality and a way forward using treatments that target HR-defective hypoxic cells. This includes the potential use of the chemotherapy drug, cisplatin, or PARP inhibitors, similar to their use in prostate or other cancers that have genetic defects in BRCA1 or BRCA2 (Luoto et al; Genome Integrity 2013).

Recently, our group, in collaboration with scientists in Melbourne, have used whole genome sequencing (WGS) to explore the genetic defects in the tissues derived from untreated localized prostate cancers that arise in men with familial BRCA2 mutation carrier status (Taylor et al; Nature Comm, Jan 2017; Boutros et al; Nature, 2017) compared to those that arise as sporadic prostate cancers. We observed activation of a number of pathways usually reserved solely for patients that acquire castrate resistance and metastasis during the progression of sporadic cancer including altered beta catenin- WNT signalling, defective mitotic control and DNA repair and altered androgen signalling. Together, these findings suggest that in untreated BRCA2-associated prostate cancers, pathways are already upregulated that herald resistance to hormone therapy and genetic instability. However the additional mechanistic role of hypoxia in the acquisition of these aggressive phenotypes on the background of BRCA1/BRCA2 genetic deficiency is not known (Lalonde et al; Lancet Oncology, 2014; Chan et al; Mol.Can Res; 2014; Chua at al; Eur Urol., 2017).
The project will develop and utilize isogenic defective in BRCA1 and BRCA2 and determine the additional effect of hypoxia on the generation of genetic instability, HR repair and sensitivity to inhibitors of DNA repair machinery including those targeting ATM, ATR and DNA-PKcs using both in vitro and in vivo systems. The effects of hypoxia on genetic instability will be explored using whole genome sequencing approaches and RNA seq. Understanding the mechanism by which hypoxia drives genetic instability in the absence and presnce of underlying DNA repair defects may allow for better patient stratification using precision medicine for optimal prostate cancer treatment.

Informal enquiries should be addressed to Professor Robert Bristow; [email protected]

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Interested students can find full group project details, entry criteria and details on how to apply on the CRUK Manchester Institute website;
http://www.cruk.manchester.ac.uk/education/PhD-Studentships

*Closing date: Friday 19 January 2018, 2400 hrs (GMT)*
*Interview date: Wednesday 14 February 2018, Alderley Park, Cheshire*

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PhD Scholarships

PhD positions at The University of Warwick : Biological Sciences/Synthetic biology (# of pos: 4)

Our group is offering PhD positions for 2018-2019 academic year.  These studentships are hosted by The University of Warwick Doctoral Training Centres 

 Details below

1) PhD project title: Engineering microbial chemical factories to produce renewable and modified biomaterials. 

PhD is hosted via MIBT Partnership

Research Area  : Synthetic biology, Organocatalysis, Structural biology and enzymology

Link :-  https://warwick.ac.uk/fac/cross_fac/mibtp/pgstudy/phd_opportunities/molecularandmetabolicengineering2018/biomaterials

2) PhD project title: Development of novel halogenase enzymes for biopharmaceutical applications.

PhD is hosted via MIBT Partnership

Research Area : Synthetic biology, Organocatalysis, Structural biology and enzymology

Link :- https://warwick.ac.uk/fac/cross_fac/mibtp/pgstudy/phd_opportunities/molecularandmetabolicengineering2018/applications

3) PhD project title: Expanding the genetic lexicon: Developing novel tools for non-natural amino acid incorporation in to therapeutic peptides and proteins.

PhD is hosted via SynBIO DTC 

Research Area : Synthetic biology, Organocatalysis, Structural biology and enzymology

Link :- https://www2.warwick.ac.uk/fac/sci/lifesci/study/pgr/studentships/synbiocdt

4) PhD project title:  Bioplastics from E. coli

PhD is hosted via SynBIO DTC

Research Area : Synthetic biology, Organocatalysis, Structural biology and enzymology

Link :- https://www2.warwick.ac.uk/fac/sci/lifesci/study/pgr/studentships/synbiocdt

Applications are encouraged from UK, EU and International students.

Please be aware that International (non EU) applicants are not eligible for EPSRC/BBSRC funded studentships.

To be eligible for a full EPSRC/BBSRC award (Tuition fees and Stipend) a student must have:

  • Settled status in the UK, meaning they have no restrictions on how long then can stay and
  • Been ‘ordinarily resident’ in the UK for 3 years prior to the start of the studentship. This means they must have been normally residing in the UK (apart from temporary or occasional absences) and
  • Not been residing in the UK wholly or mainly for the purpose of full-time education. (This does not apply to UK or EU nationals).
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To be eligible for an EPSRC/BBSRC tuition fees only award:

  • Students from EU countries other than the UK are generally eligible for a fees-only award. To be eligible for a fees-only award, a student must be ordinarily resident in a member state of the EU, in the same way as UK students must be ordinarily resident in the UK.

Interested students with research experience and qualification please contact us directly. 

https://warwick.ac.uk/fac/sci/lifesci/people/bmenon/

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France Scholarships

PhD position in quantum optimal control theory at the University of Bourgogne

This PhD project aims at applying innovative mathematical tools coming

from optimal control theory to improve theoretical and experimental techniques

in Nuclear Magnetic Resonance (NMR), in Electron Spin Resonance (ESR) and in NV

centers. This approach will allow us to explore and to experimentally reach the

physical limits of the corresponding spin dynamics in presence of typical

experimental imperfections and limitations. A first objective will be to

develop new optimal control algorithms able for an inhomogeneous ensemble of

spins to maximize the signal to noise ratio per unit time of the system. A

general problem is to generalize the Ernst angle solution used in NMR, which is

only valid for a homogeneous spin ensemble. This work will be done in

collaboration with the group of S. Glaser (TUM, Munich, Germany). This approach

will find different applications in NMR and ESR where the sensitivity of the

experiment is a crucial parameter. The student will focus on a specific

experimental setup in ESR used by the group of P. Bertet (CEA, Paris Saclay),

where an important goal is the maximization of the emitted signal of spins

coupled to a microwave resonator. The student will take into account in the

numerical computation specific constraints of this experimental setup. In the

same direction, the student will also use optimal control techniques to design

new CMPG sequences accounting for the coupling between the spins and the

cavity. The same types of control techniques will also be used for manipulating

NV ensembles in collaboration with the group of T. Debuisschert (Thalès,

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Paris). This will allow the improvement of the sensitivity of the corresponding

experiments. For a more fundamental point of view, the ESR will investigate the

numerical techniques used to design robust control fields with respect to

experimental imperfections. A first objective will be to understand the

efficiency of these methods and to prove the optimality (this concept will be

to define rigorously) of the control fields. The ESR will mainly study spin

systems but it is clear that the results of this project will not be restricted

to the physical systems investigated and the techniques developed during the

PhD could be applied to other physical systems with similar properties.

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Israel Scholarships

Marie Curie Innovative Training Network (ITN) META-CAN – PhD position in Computational biology to…

The Machine Learning for Healthcare and Life Sciences group at IBM Research – Haifa is a partner in the funded Marie Curie Innovative Training Network (ITN) META-CAN. The network is a pan-European interdisciplinary and intersectoral training programme for excellence.  It brings young researchers together with world-leading academics, clinicians, and industry personnel to focus on the connections of metabolism, immune response, and cancer.

We are looking for an enthusiastic and highly-motivated early stage researcher (ESR), with a background and experience in computational biology, machine learning and/or statistics and good programming skills (preferably in Python or R). This ESR will study towards a PhD degree and, under our guidance (and in collaboration with the Technion Integrated Cancer Center), will analyze comprehensive omics data to better understand the metabolic adaptations of cancer cells to the central nervous system niche.

The right candidate will enjoy a competitive salary and outstanding work environment.

For more details see http://metacan.eu/  or contact [email protected]

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