Program BioLAB

Informacje dla absolwentów i absolwentek

Oferty pracy

Jeśli chcesz, żebyśmy opublikowali tutaj ofertę pracy, która może zainteresować absolwentów i absolwentki programu BioLAB, wyślij ją do koordynatorki – Patrycji Donaburskej ([email protected]).

Data publikacji: 10 stycznia 2022

Project leader: Matthias P. Mayer
Application Deadline: until position is filled
Start of PhD project: as soon as possible
Source of Funding: DFG

Project Description: Cells are frequently exposed to stressful conditions due to physical or chemical changes in the environment, like changing temperatures, pH, heavy metals, reactive oxygen species (ROS), or toxic compounds, or due to physiological changes intrinsic to differentiation and development, or due to pathophysiological changes during an assault of pathogens. To cope with such conditions a transcriptional program developed early in evolution, called the heat shock response (HSR). Central to the HSR in all eukaryotic cells is the heat shock transcription factor (Hsf1) that up-regulates transcription of a specific set of genes encoding components of the cellular quality control system like molecular chaperones and proteases. Hsf1 also plays a pivotal role in many human diseases like cancer and neurodegenerative pathologies including Parkinson s disease and Ataxias. The central theme of the here advertised two positions is to further our understanding of the molecular mechanism of the regulation of Hsf1, to lay the ground work for future developments of drugs that might activate or inhibit Hsf1 to ameliorate the treatment of the above-mentioned diseases. In previous studies in our lab we could show that Hsf1 is a thermosensor that reacts to the amount of heat absorbed from the environment by transiting from the monomeric to the trimeric state that is capable of binding to DNA and driving transcription. We could further show that Hsp70 chaperones regulate Hsf1 in a negative feedback loop by actively monomerizing the Hsf1 trimers and thereby dissociating them from DNA. However, there are still many questions open.

The successful candidates will analyze the interaction of HSF1 with molecular chaperones and cochaperones in vivo using cell culture model systems and in vitro using purified proteins and biochemical and biophysical methods.

References:
Hentze, N., Le Breton, L., Wiesner, J., Kempf, G. & Mayer, M.P. Molecular mechanism of thermosensory function of human heat shock transcription factor Hsf1. eLife 5:e11576 (2016); doi: 10.7554/eLife.11576
Kmiecik, S.W., Le Breton, L. & Mayer, M.P. Feedback regulation of heat shock factor 1 (Hsf1) activity by Hsp70-mediated trimer unzipping and dissociation from DNA. The EMBO Journal 39:e104096 (2020); doi: 10.15252/embj.2019104096
Kmiecik, S.W., Drzewicka, K., Melchior, F. & Mayer, M.P. Hsf1 is SUMOylated in the activated trimeric state. Journal of Biological Chemistry 296, 100324 (2021); doi: 10.1016/j.jbc.2021.100324

Methods that will be used:
Fluorescence microscopy, life cell imaging, immunoprecipitation, protein purification, in vivo and in vitro protein-protein-interaction assays, fluorescence spectroscopy, hydrogen exchange mass spectrometry, protein-DNA interaction assays (EMSA, fluorescence polarization)

https://www.zmbh.uni-heidelberg.de/Mayer/open.html

Data publikacji: 11 stycznia 2022

Project leader: Dr Thomas Iskratsch
Application Deadline: until position is filled
Start of PhD project: September 1
Source of Funding: UKRI EPSRC

Project Description:

Heart failure (HF) is a major cause of death in the UK. New therapies are urgently needed but their development has been hindered by the still limited understanding of the biological basis. Apart from genetic and humoral factors, the mechanical/physical signals are critically involved in the process.

Especially, the cardiac extracellular matrix (ECM) stiffens in heart disease, which drives disease progression. However, not only the stiffness, but also changes in ECM composition will alter the downstream mechanosignalling. Better understanding of the mechanobiology can open new perspectives for treating heart failure. Therefore, novel tools are needed to help understand the complexity of both stiffness and receptor ligand architecture in heart disease.

We previously investigated cardiomyocyte mechanosensing (Pandey et al, Developmental Cell, 2018) and adhesion formation, for which we developed biomimetic nanoarrays (here: nanobioarrays), based on nanopatterned DNA origami (Hawkes et al, Faraday Discussions, 2019). Using our new NanoFrazor Explore thermal-scanning probe lithography tool, we are now able to pattern on surfaces with different stiffness. This way we can generate next-generation nanobioarrays to enable quantitative measurement of changes to adhesion composition in response to the precisely defined presence and relative abundance of specific receptor ligands, as well as the stiffness of the environment. Especially, we seek here to develop nanobioarrays with tunable stiffness and different ratios of integrin ligands for extracellular matrix components that are present in the healthy and diseased myocardium in order to study the implications on downstream adhesion signalling and identify druggable modifiers of the mechanosignalling. For this the student will:

  1. Develop next-generation nanobioarrays with tunable stiffness and defined integrin ligand configuration
  2. Analyse the adhesion composition depending on stiffness and receptor ligand configuration
  3. Analyse the mechanosignalling (e.g. active integrin, pSrc, pFAK, YAP, etc) depending on stiffness and receptor ligand configuration
  4. Screen for modulators of mechanosignalling

Funding

This studentship is fully funded via the UKRI EPSRC Doctoral Training Programme for 3.5 years and includes a stipend (currently £17,609 in 2021/2022) and Fees.

Eligibility

This year UKRI announced that there will be a limited number of studentships for international students available. International applicants are encouraged to apply but should note that studentship awards will be subject to eligibility and the availability of funding.

To be classed as a home student, applicants must meet the following criteria:

  • Be a UK National (meeting residency requirements), or
  • Have settled status, or
  • Have pre-settled status (meeting residency requirements), or
  • Have indefinite leave to remain or enter

If a candidate does not meet the criteria above, they would be classified as an international student.

Further guidance on UKRI Eligibility Criteria is here, and within Annex One of the International Eligibility Guidance.

  • The minimum requirement for this studentship opportunity is a good Honours degree (minimum 2(i) honours or equivalent) or MSc/MRes in a relevant discipline.
  • If English is not your first language, you will require a valid English certificate equivalent to IELTS 6.5+ overall with a minimum score of 6.0 in Writing and 5.5 in all sections (Reading, Listening, Speaking).
  • Candidates are expected to start from September 2022

Application Method:

To apply for this studentship and for entry on to the PhD Full-time Medical Engineering – Semester 1 (September Start) please follow the instructions detailed on the following webpage:

Research degrees in Engineering:​ http://www.qmul.ac.uk/postgraduate/research/subjects/engineering.html

Further Guidance: http://www.qmul.ac.uk/postgraduate/research/

Please be sure to include a reference to ‘2022 EPSRC DTP TI’ to associate your application with this studentship opportunity.

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