Cellular logistics: Biological physics of selective protein and gene transport across the nuclear envelope

The coordinated transport of proteins and nucleic acids between the nucleus and the cytosol is vital for proper gene expression and cell function, and hijacked by viruses to propagate. In this PhD project, you will devise new methods to study the physical and molecular mechanisms that make transport selective. This is a formidable challenge that requires multiple disciplines, physics, biology and chemistry, to work hand in hand.<br /> <br /> The hallmark of eukaryotic cells is the their compartmentalisation into the nucleus, which harbours our genes, and the cytosol in which the genetic code is translated into functional proteins. This spatial separation enables sophisticated regulation, but also poses a tremendous logistical challenge to the cell as nucleic acids and proteins have to be shuttled across the nuclear envelope. Macromolecular transport occurs through 40 nm wide channels in nuclear pore complexes that perforate the nuclear envelope. Transport is gated by the nuclear pore permselectivity barrier, a meshwork of intrinsically disordered proteins and transport receptors that fills the channels; yet, how this meshwork enables rapid yet highly selective transport is not well understood.<br /> <br /> In a multidisciplinary environment, you will learn to create bottom up biosynthetic models of the permselectivity barrier and develop advanced optical microscopy techniques to track molecular transport within these nanoscale barriers. The experimental work will be accompanied by theoretical work to aid the analysis of the experimental data and develop an understanding of the molecular and soft matter physics underpinning selective nucleo-cytoplasmic transport.<br /> <br /> In this project, you will put physics and chemistry tools to the benefit of understanding biology. This will provide new insight into how nucleo-cytoplasmic transport is regulated, and ultimately help to devise new strategies to interfere with diseases, such as viral infection, and to design advanced biomaterials (e.g. for biosensors).<br /> <br /> Suitable CANDIDATES would have a background in biophysics, soft matter physics, physical chemistry, biomedical engineering or a closely related field, and keen interest in multidisciplinary work. Experience in advanced optical microscopy and/or in scientific programming are an advantage.

<div class="cms"> <p><strong>Physics and Biological Sciences at Leeds.</strong> The University of Leeds (UoL) operate low-wall&nbsp;principles with the aim of encouraging cross-disciplinary approaches to big science questions. This project will take place in the&nbsp;<a href="https://eps.leeds.ac.uk/physics-research-groups/doc/molecular-nanoscale-physics">Molecular and Nanoscale Physics Group</a>&nbsp;within the <a href="https://eps.leeds.ac.uk/physics">School of Physics and Astronomy</a>, in tight collaboration with&nbsp;the <a href="https://biologicalsciences.leeds.ac.uk/">Faculty of Biological Sciences</a>. The <a href="https://biologicalsciences.leeds.ac.uk/school-biomedical-sciences/staff/129/dr-ralf-richter">Richter Lab</a> is also part of the <a href="https://www.leeds.ac.uk/info/130565/bragg_centre_for_materials_research">Bragg Centre for Materials Research</a>, and the <a href="https://www.astbury.leeds.ac.uk/">Astbury Centre for Structural Molecular Biology</a>.&nbsp;This environment offers&nbsp;superb facilities, provides a high quality research training&nbsp;and delivers an exceptional student education.</p> <p><strong>Collaboration with other research institutes.</strong> The successful applicant will be hosted by the <a href="https://biologicalsciences.leeds.ac.uk/school-biomedical-sciences/staff/129/dr-ralf-richter">Richter Lab</a> at UoL. This project is part of a collaboration with the <a href="https://www.mpibpc.mpg.de/goerlich">Department of Cellular Logistics</a> at the Max Planck Institute for Biophysical Chemistry, Germany, and ITMO University, Russia.</p> <p><strong>References</strong></p> <ol> <li> <p>R. Zahn, D. Osmanovic, S. Ehret, C. Araya Callis, S. Frey, M. Stewart, C. You, D. Gorlich, B. W. Hoogenboom and R. P. Richter (2016) A physical model describing the interaction of nuclear transport receptors with FG nucleoporin domain assemblies. <em>eLife</em> 5:e14119.</p> </li> <li> <p>R. Frost, D. Debarre, S. Jana, F. Bano, J. Schunemann, D. Gorlich and R. P. Richter (2020) A method to quantify molecular diffusion within thin solvated polymer films: A case study on films of natively unfolded nucleoporins. <em>ACS Nano</em> 14:9938.</p> </li> </ol> </div>

<div class="cms"> <p>Formal applications for research degree study should be made online through the&nbsp;<a href="https://www.leeds.ac.uk/research-applying/doc/applying-research-degrees">University&#39;s website</a>. Please state clearly in the Planned Course of Study that you are applying for <em><strong>PHD Physics &amp; Astronomy FT,</strong></em>&nbsp;in the research information section&nbsp;that the research degree project you wish to be considered for is <em><strong>Cellular logistics: Biological physics of selective protein and gene transport across the nuclear envelope </strong></em>as well as Dr Ralf Richter&nbsp;as your proposed supervisor&nbsp;and in the finance section, please state clearly&nbsp;<em><strong>the funding that you are applying for, if you are self-funding or externally sponsored</strong></em>.</p> <p>Profiles:&nbsp; <a href="https://eps.leeds.ac.uk/physics/staff/4129/dr-ralf-richter">Dr Ralf Richter (Physics &amp; Astronomy)</a>, <a href="https://biologicalsciences.leeds.ac.uk/school-biomedical-sciences/staff/129/dr-ralf-richter">Dr Ralf Richter (Biological Sciences)</a></p> <p>If English is not your first language, you must provide evidence that you meet the University&#39;s minimum English language requirements (below).</p> <p style="margin-bottom:11px"><em>As an international research-intensive university, we welcome students from all walks of life and from across the world. We foster an inclusive environment where all can flourish and prosper, and we are proud of our strong commitment to student education. Across all Faculties we are dedicated to diversifying our community and we welcome the unique contributions that individuals can bring, and particularly encourage applications from, but not limited to Black, Asian, people who belong to a minority ethnic community, people who identify as LGBT+ and people with disabilities. Applicants will always be selected based on merit and ability.</em></p> <p class="MsoNoSpacing">Applications will be considered on an ongoing basis. &nbsp;Potential applicants are strongly encouraged to contact the supervisors for an informal discussion before making a formal application. We also advise that you apply at the earliest opportunity as the application and selection process may close early, should we receive a sufficient number of applications or that a suitable candidate is appointed.</p> <p class="MsoNoSpacing">Please note that you must provide the following documents in support of your application by the closing date of 3 April 2024 for Leeds Opportunity Research Scholarship or 8 April 2024 for Leeds Doctoral Scholarship:</p> <ul> <li>Full Transcripts of all degree study or if in final year of study, full transcripts to date</li> <li>Personal Statement outlining your interest in the project</li> <li>CV</li> </ul> </div>

Applicants to research degree programmes should normally have at least a first class or an upper second class British Bachelors Honours degree (or equivalent) in an appropriate discipline. The criteria for entry for some research degrees may be higher, for example, several faculties, also require a Masters degree. Applicants are advised to check with the relevant School prior to making an application. Applicants who are uncertain about the requirements for a particular research degree are advised to contact the School or Graduate School prior to making an application.

The minimum English language entry requirement for research postgraduate research study is an IELTS of 6.0 overall with at least 5.5 in each component (reading, writing, listening and speaking) or equivalent. The test must be dated within two years of the start date of the course in order to be valid. Some schools and faculties have a higher requirement.

<div class="cms"> <p style="margin-bottom:12px"><strong>Self-Funded or externally sponsored students are welcome to apply.</strong></p> <p><strong>UK</strong>&nbsp;&ndash;&nbsp;The&nbsp;<a href="https://phd.leeds.ac.uk/funding/209-leeds-doctoral-scholarships-2022">Leeds Doctoral Scholarships</a> and <a href="https://phd.leeds.ac.uk/funding/234-leeds-opportunity-research-scholarship-2022">Leeds Opportunity Research Scholarship</a> are available to UK applicants. The&nbsp;<a href="https://phd.leeds.ac.uk/funding/102-bell-burnell-scholarship-award-awarded-by-the-iop">Bell Burnell Scholarship Award</a>&nbsp;is available to support applicants who are from groups that are currently under-represented in physics (awarded by the IOP) (now closed for 2024/25 entry).&nbsp; <a href="https://phd.leeds.ac.uk/funding/60-alumni-bursary">Alumni Bursary</a> is available to graduates of the University of Leeds.</p> <p><strong>Non-UK</strong> &ndash; The&nbsp;<a href="https://phd.leeds.ac.uk/funding/48-china-scholarship-council-university-of-leeds-scholarships-2021">China Scholarship Council - University of Leeds Scholarship</a>&nbsp;is available to nationals of China (now closed for 2024/25 entry). The&nbsp;<a href="https://phd.leeds.ac.uk/funding/73-leeds-marshall-scholarship">Leeds Marshall Scholarship</a>&nbsp;is available to support US citizens. <a href="https://phd.leeds.ac.uk/funding/60-alumni-bursary">Alumni Bursary</a> is available to graduates of the University of Leeds.</p> <p><strong>Important:</strong>&nbsp; Any costs associated with your arrival at the University of Leeds to start your PhD including flights, immigration health surcharge/medical insurance and Visa costs are <strong>not</strong> covered under these studentships.</p> <p>Please refer to the <a href="https://www.ukcisa.org.uk/">UKCISA</a> website for information regarding Fee Status for Non-UK Nationals.</p> </div>

<div class="cms"> <p>Individuals interested in this project are encouraged to contact Dr. Ralf Richter (<a href="mailto:r.richter@leeds.ac.uk">r.richter@leeds.ac.uk</a>) for further information.&nbsp;We are always happy to discuss scientific questions with pro-active candidates.</p> <p>For questions related to the application process and eligibility, please contact Doctoral College Admissions by email (<a href="mailto:maps.pgr.admissions@leeds.ac.uk">maps.pgr.admissions</a><a href="mailto:EMAIL@leeds.ac.uk">@leeds.ac.uk</a>)&nbsp;</p> </div>