[ccp4bb] post-doctoral position at VIB-Plant Systems Biology, Belgium.

[Savvas Savvides]

Within the framework of an ERC Consolidator project, an initial 2-year 
postdoctoral position is available in the Advanced Live Cell Imaging group of 
Daniel Van Damme at The VIB/UGent Department of Plant Systems Biology to 
investigate the ultrastructure of the plant endocytic TPLATE complex (TPC).

The TPC has its evolutionary origins between the emergence of COPI and the 
functional specification of the AP complexes. While the TPC remained essential 
for plants, it was evolutionarily lost in yeasts and animal cells, indicating 
that endocytosis operates differently in plants (Gadeyne et al., Cell 2014: 
Hirst et al., Elife 2014). The project aims to generate structural and 
mechanistic insights into membrane recruitment and cargo identification of the 
TPC as well as its interplay with the evolutionarily conserved AP-2 complex. 
The project will run in close collaboration with structural biology groups 
within the VIB institute (Savvas Savvides, VIB/UGent and Rouslan Efremov, 
VIB/VUB).

The successful candidate will spearhead the structural elucidation of an 
enigmatic endocytic complex and will become part of a lively research group 
with a long track record on unravelling the role of this key endocytic complex 
in plants (Van Damme et al., Plant Journal 2004; Van Damme et al., Plant Cell 
2006; Van Damme et al PNAS 2011; Gadeyne et al., Cell 2014).

Motivated candidates with a PhD and a proven track record in structural biology 
and/or molecular biology (e.g. protein/complex purification, recombinant 
protein biochemistry, X-ray crystallography, single-particle EM etc) are 
requested to send their CV (including academic record, publications and proof 
of relevant experience), a statement of interest focusing on the project and 
the contact details of two referees (name, organization, phone, e-mail address) 
to:

daniel.vanda...@psb.vib-ugent.be  

Prior experience in the field of endocytosis is an asset. The succesful 
candidate can start immediately and the call will remain open until a suitable 
candidate is found. Selected candidates will be invited for an interview or 
skype meeting.



 

[ccp4bb] PhD Studentship in mTORC1 Signalling in Autophagy and Ageing

[Owen Davies]

Dear colleagues,

A 3.5-year PhD studentship is available to study the molecular mechanism of 
mTORC1 signalling in autophagy, cellular ageing and age-related diseases 
through an interdisciplinary approach of biochemistry, biophysics, X-ray 
crystallography and cellular biology. It will be based in my lab and will 
include an extended rotation period with Dr Viktor Korolchuk, in Newcastle. The 
details of the project are as follows:

The molecular mechanism of mTORC1 signalling in autophagy, cellular ageing and 
age-related diseases through biochemistry, structural biology and cellular 
biology
The mammalian 'Target of Rapamycin Complex' (mTORC1) controls cellular growth 
and proliferation in response to nutrient availability. This fundamental 
cellular signalling mechanism permits growth of cells when sufficient nutrients 
(particularly amino acids) are present, and is thereby essential for the growth 
of our cells and tissues (Bar-Peled and Sabatini 2014, Trends Cell Biol). 
However, this same mechanism can become detrimental during ageing, when TORC1 
signalling contributes to organismal decline and age-related diseases such as 
Alzheimer's disease, heart disease and cancer (Laplante and Sabatini 2012, 
Cell). Indeed, the relevance of mTORC1 signalling to ageing has been 
highlighted by interventions such as calorie restriction or rapamycin 
treatment, which suppress this pathway and have been shown to extend life-span 
and prevent age-related illnesses. In such cases, nutrient starvation or direct 
inhibition trigger autophagy, a process of self-degradation in which damaged 
cellular material is removed and recycled to allow the repair of tissues.

This PhD project aims to understand how amino acids are recognised by the 
mTORC1 machinery and how this results in activation of the pathway. We have 
identified a novel mechanism of mTORC1 activation by amino acids which act by 
blocking the inhibition of master mTORC1 activator Rheb by negative regulator 
TSC2 (Carroll et al 2016, eLife). This simple signalling pathway has numerous 
possibilities for exploitation in the new therapeutics that may slow or delay 
the development of age-related diseases, and so this PhD project aims to 
uncover the precise molecular mechanism whereby this process is achieved. We 
will use a combination of biochemical, structural biology and cellular biology 
methods to determine the atomic resolution structure of the TSC2-Rheb complex, 
the basis of its inhibition by amino acids, and the molecular mechanism whereby 
Rheb activates mTORC1 within the cell.

This interdisciplinary PhD project will be based in the laboratories of Dr Owen 
Davies and Dr Viktor Korolchuk in the Institute of Cell and Molecular 
Biosciences, Newcastle University, and will provide an unprecedented level of 
training in a wide variety of techniques. These will include molecular cloning, 
recombinant protein expression and purification, biophysical methods (including 
SEC-MALS, SEC-SAXS, ITC, MST, CD and EM) and X-ray crystallography, in addition 
to mammalian cell culture, genetic modification of cell lines, 
immunofluorescence and flow cytometry.

This project will provide a crucial step towards being able to manipulate 
mTORC1 and its deregulation in ageing. We envisage that this will catalyse 
future translational research into therapeutic targeting of age-related 
disease, which will have clear and fundamental implications for medicine.

Funding details
MRC DiMeN DTP studentships are funded for 3.5 years and include:
Tax-free maintenance grant set at the UK Research Council's national rate.
Full payment of tuition fees at the Home/EU rate.
A Research Training Support Grant to support your research studies.

Successful Home students will receive a full studentship. EU students will be 
considered for a full studentship/fees only support depending on the excellence 
of their qualifications and their employment/residency status.

Advert website
https://www.findaphd.com/search/ProjectDetails.aspx?PJID=80881=3415

To apply
For more information about the PhD programme and to apply please visit the 
DiMeN website:
http://www.dimen.org.uk/

Closing date for applications
6th January 2017

Please also feel free to contact me directly with any further queries.

Best wishes,

Owen Davies.

Dr Owen Davies
Wellcome Trust and Royal Society Sir Henry Dale Fellow
Institute for Cell and Molecular Biosciences
Faculty of Medical Sciences
Newcastle University
United Kingdom

Telephone: +44 (0)191 208 7371
e-mail: owen.dav...@newcastle.ac.uk
website: http://www.ncl.ac.uk/camb/staff/profile/owen.davies

[ccp4bb] PhD Studentship in Meiotic Chromosome Structure and Recombination

[Owen Davies]

Dear colleagues,

A four-year PhD studentship is available to study meiotic chromosome structure 
and recombination through biochemistry, biophysics, X-ray crystallography and 
bioinformatics. It will be based in my lab in Newcastle and will include an 
extended rotation period with Dr Dan Rigden in Liverpool. The details of the 
project are as follows:

The molecular structure and function of the synaptonemal complex in chromosome 
synapsis and recombination during meiosis
Meiosis, the process of reductive cell division, is essential for fertility and 
genetic diversity in all sexually reproducing organisms. At the centre of this 
process is the synaptonemal complex (SC), a protein superstructure that acts a 
molecular 'zipper' to bind together homologous chromosomes along their entire 
length. The three-dimensional architecture of the SC imposes the necessary 
chromosomal structure and provides the physical framework for meiotic 
recombination and crossover formation. These processes are achieved through 
homologous recombination-mediated DNA double-strand break repair pathways, and 
are essential for fertility. Defects in synaptonemal complex formation lead to 
infertility, recurrent miscarriage and aneuploidies such as Down's syndrome, in 
addition to germline cancers. However, whilst the protein building blocks of 
the synaptonemal complex have been identified in both humans and yeast, the 
structure of the complex and its molecular function in meiosis remain unknown.

This PhD project aims to elucidate the molecular structures of the principal 
yeast SC components Zip1 and Ecm11-Gmc2, and to determine their mechanism of SC 
assembly. This will be achieved through recombinant protein purification, a 
range of biophysical techniques (including SEC-MALS, SEC-SAXS, CD and EM), 
X-ray crystallography, yeast two-hybrid and genetics, and computational 
bioinformatics. It will therefore involve an unprecedented level of 
multi-disciplinary training. We will combine the resulting molecular 
information with our ongoing studies on the human SC to define the underlying 
molecular basis for SC function across eukaryotes. This will enable us to 
translate directly between human and yeast systems, allowing us to exploit the 
genetic tractability of yeast in a manner that is directly applicable to our 
understanding of human fertility. Ultimately, we aim to engineer a chimeric 
system in which a humanised SC is assembled and functional in yeast, and thus 
establish a truly genetically tractable cellular system for studying a full 
human SC in vivo.

The PhD studentship is cross-institutional, and will be based primarily at 
Newcastle University, with Liverpool University hosting an extended rotation 
period and providing support as necessary throughout for the bioinformatics 
work. The project will be supervised by Dr Owen Davies (Newcastle) and Dr Dan 
Rigden (Liverpool), and is part of a collaboration with EM tomography, genetics 
and cellular biology groups within the institute and worldwide, with whom we 
will test our biochemical and crystallographic findings in cellular models. 
This project should result in highly publishable and high impact research 
findings in the fields of meiotic cell division, chromosomal biology and X-ray 
crystallography. The successful candidate will be a highly motivated individual 
with interests in solving fundamental molecular questions of cellular function 
through both practical structural biology and computational approaches.

Funding details
This is a 4 year BBSRC studentship under the Newcastle-Liverpool-Durham DTP. 
The successful applicant will receive research costs, tuition fees and stipend 
(£14,296 for 2016-17). The PhD will start in October 2017. Applicants should 
have, or be expecting to receive, a 2.1 Hons degree (or equivalent) in a 
relevant subject. EU candidates must have been resident in the UK for 3 years 
in order to receive full support. There are 2 stages to the application process.

Advert website
https://www.findaphd.com/search/ProjectDetails.aspx?PJID=80667=1120

To apply
Please submit a full CV and covering letter directly to 
owen.dav...@newcastle.ac.uk

Please also feel free to contact me directly with any further queries.

Best wishes,

Owen Davies.

Dr Owen Davies
Wellcome Trust and Royal Society Sir Henry Dale Fellow
Institute for Cell and Molecular Biosciences
Faculty of Medical Sciences
Newcastle University
United Kingdom

Telephone: +44 (0)191 208 7371
e-mail: owen.dav...@newcastle.ac.uk
website: http://www.ncl.ac.uk/camb/staff/profile/owen.davies