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Applications are invited for 4-year PhD studentship based in the Department of Physiology, Development and Neuroscience and the MRC Toxicology unit in the School of Biological Sciences at U. of Cambridge and the new AstraZeneca Discovery Centre at Cambridge. The student will be working on a collaborative project jointly supervised by Dr Mennella in in the MRC Toxicology Unit and Dr Emma Rawlins in Department of Physiology, Development and Neuroscience in the School of Biological Sciences at U. of Cambridge and Dr Jennifer Tan, Dr Benedicte Recolin, Dr Kelly Evans and Dr Catherine Betts at AstraZeneca and will have the opportunity to work across the two sites. The project, entitled "Unravelling and predicting toxicity of Antibody Drug Conjugates in the lung using genome-wide multi-omics and CRISPR-Cas9" aims at leveraging knowledge in airway biology and Omics technologies to understand why Antibody Drug Conjugates, a promising new drug modality with high efficacy against lethal cancers can cause adverse response limiting their use. This is an important area of applied research that has generated much excitement in both academia and industry.

Project Abstract:

Antibody-drug conjugates (ADCs) are promising oncology agents targeting both solid tumours and haematological malignancies with high target specificity and killing efficiency. ADCs consists of a small molecule cytotoxin (payload) attached to a monoclonal antibody (mAb) carrier. In recent years, a handful of blockbuster ADCs have been approved by the FDA, and currently over 400 drugs are in the pipeline, rapidly transforming healthcare. However, clinical toxicities limit their full potential. In particular, pulmonary toxicities, (i.e. Interstitial Lung Disease (ILD)), which can be potentially fatal, has been reported in the clinic ¿ e.g. ILD has been reported for T-Dxd, an ADC consisting of anti-Her2 antibody/anti- topoisomerase 1 inhibitor conjugate (15.8% with 2% fatal rate). Importantly, to date, no biomarker and/or screening assay is available for safety screening and assessment. Mechanisms underlying ADC-induced lung toxicities are believed to be complex, mediated primarily through ADC uptake by alveolar macrophages, which may crosstalk with epithelial cells, leading to scarring and remodeling. However, the underlying molecular cascade remains unknown. To maximize the full potential of ADC therapeutics, urgent new information is required to understand off-target toxicities of ADCs and how different components of the ADCs may be modified to mitigate their toxicity (antibody, linker, payload). The project proposes a data-driven approach using multi-omics and CRISPR-Cas9 screening using airway models to investigate the molecular mechanisms underpinning ADC lung toxicity.

Candidate:

We are looking for a highly motivated and enthusiastic individual capable of thinking and working independently. Applicants should have or shortly expect to obtain a first or upper second-class degree from a UK university, or an equivalent standard from an overseas university, in a relevant subject such as Cell Biology, Molecular Biology and Biochemistry. Interest in bioinformatics and omics data analysis is preferred but not required. These positions are open to UK citizens or overseas students who meet the UK residency requirements (home fees) or are able to augment the funds to cover the extra costs associated with international student fees through scholarships or funding schemes. Full details of the University's entrance requirements and scholarships are specified on the following link: https://www.postgraduate.study.cam.ac.uk/

Funding

Full funding covering Maintenance fees at £21,500 per annum and the University Composition Fee is provided for the studentship, with effect from 1 October 2024.

Deadline Deadline for applications is 8th January and interviews will be held in early January.

Please quote reference PR39642 on your application and in any correspondence about this vacancy.

How to apply: Please send a covering letter that describes your previous research experience and motivation for the project, your CV with your University grades, your academic transcripts and the names and contact details of two academic referees who have agreed to act on your behalf to Dr Vito Mennella via email (vm430@cam.ac.uk). For important queries related to the PhD studentship contact Dr Vito Mennella, vm430@cam.ac.uk.

The University actively supports equality, diversity and inclusion and encourages applications from all sections of society.

The University has a responsibility to ensure that all employees are eligible to live and work in the UK.

Student support and training

As a graduate student at Cambridge, you will have access to a wide range of training opportunities and benefit from close supervision provided by a primary and secondary PhD supervisor as well as a personal mentor. During their PhD, there is no taught or examined coursework, but students are encouraged to attend the wide variety of lectures and training courses available to them across the Institute and wider University. This includes a centrally run Statistics course and the University Core Skills Training Programme, which includes sessions on Time Management, Presentation and Performance and Scientific Writing. Students at the Institute will be members of the University's Postgraduate School of Life Sciences (PSLS) who offer a wide variety of core skills and professional development training. Visit the Researcher Development page on the PSLS website for more information. In addition, the student can also take advantage of training courses and seminars in therapeutic sciences offered by Cambridge Academy of Therapeutic Sciences. All students are expected to attend all internal and external seminars held within the Department of Physiology, Development and Neuroscience and the MRC Toxicology Unit. Students will also be encouraged to attend and present at the annual AstraZeneca students symposium.

Diversity and Inclusion

The University actively supports equality, diversity and inclusion and encourages applications from all sections of society. We place major emphasis on the importance of team work and an enjoyable work environment as a foundation for performing internationally leading research. This will allow the student to acquire cutting edge research methodologies in a supportive environment, where they can focus on making the best possible scientific progress.

The Gurdon Institute www.gurdon.cam.ac.uk is a vibrant, world-leading centre for research at the interface between developmental biology and cancer biology, supported by Wellcome and Cancer Research UK.

The Gurdon Institute Imaging Facility (GIIF) provides all scientists within the Gurdon Institute and the wider scientific and engineering community of the University of Cambridge with access to high-end light microscopy equipment and experimental support from sample preparation and image acquisition through to image processing and analysis.

We are looking for an imaging specialist to strengthen our capability to offer light microscopy and image analysis support as we acquire new equipment and continue to increase the variety of expertise available within the GIIF. The Imaging Specialist will assist the Imaging Facility Manager in a part time role to maintain and expand the GIIF's capabilities to support light-sheet microscopy and high-throughput plate scanning technologies in addition to the confocal and widefield modalities already well established within the GIIF. The post holder will be involved in the regular quality control (QC) and maintenance routines within the GIIF, including the administration of the microscope service contracts. Maintenance will involve interaction with the manufacturers and external field service engineers of the microscopes and ancillary equipment. The post holder will be required to troubleshoot the equipment where appropriate.

Candidates should ideally possess a PhD in the fields of biology or optical physics with practical experience of designing and performing light microscopy imaging experiments. Experience in training other users in light microscopy techniques is also highly desirable. Experience with a range of image acquisition, processing and analysis software would also be expected.

Limited funding: The funds for this post are available until 30 November 2024 in the first instance.

Applications are welcome from internal candidates who would like to apply for the role on the basis of a secondment from their current role in the University.

We welcome applications from individuals who wish to be considered for part-time working or other flexible working arrangements.

Click the 'Apply' button below to register an account with our recruitment system (if you have not already) and apply online.

Please quote reference PR39226 on your application and in any correspondence about this vacancy.

If you have any questions relating to this vacancy or application process, please contact hr@gurdon.cam.ac.uk

The University actively supports equality, diversity and inclusion and encourages applications from all sections of society.

The University has a responsibility to ensure that all employees are eligible to live and work in the UK.

We are looking for a highly motivated post-doctoral bioinformatian to join the laboratory of Dr. Sumru Bayin at the Gurdon Institute, University of Cambridge. You will work in the Bayin Lab to explore the molecular mechanisms that regulate the regenerative potential of stem cells in the brain during development and in adulthood using single cell genomics and collaborating with the wet laboratory scientists in the group.

The Bayin Lab is interested in identifying the molecular mechanisms that regulate self-renewal, differentiation and plasticity of neural stem/progenitor populations during development and homeostasis, in order to discover how to stimulate repair of the brain upon injury. The cerebellum, which is a folded hindbrain structure that is important for skilled motor movements and higher order cognitive functions, has emerged as a powerful system to study the regenerative responses in the brain. We have previously shown that the cerebellum can recover from the loss of at least two types of neurons via distinct regenerative mechanisms (Wojcinski, Nature Neuroscience, 2017; Bayin, eLife, 2018; Bayin, Science Advances, 2021, Bayin and Joyner, Development, 2022). However, the full repertoire of molecular and cellular mechanisms that regulate neonatal cerebellar development and injury response remain to be studied. Importantly, the regenerative potential of the neonatal cerebellum dramatically decreases once development ends, despite the presence of stem-like cells in the adult mouse cerebellum. This project involves using in vivo and in vitro approaches to identify mechanisms that control the developmental and regenerative responses of cerebellar progenitors in neonates and determine how it differs in adults in order to understand how we can facilitate efficient repair after injury to the brain. A variety of other projects on neural stem cell biology during brain development and pathologies are possible, depending on the candidate's interest and background. For more information, please visit: https://www.bayinlab.com

Applicants must have (or expect to obtain) a PhD (or equivalent) in biological sciences and bioinformatics. Importantly, we are looking for a highly motivated and enthusiastic team member who is a critical thinker and can work independently, and have excellent communication skills with the ability to work collaboratively within and outside of the laboratory, and promote positive research culture within the laboratory. Candidates are expected to work independently and interact well in a dynamic multidisciplinary team environment. They must display abilities in methods development and project management, and be able to communicate ideas and results clearly.

The Wellcome/Cancer Research UK Gurdon Institute is a world-renowned centre of Developmental biology and Cancer research embedded in the University of Cambridge. It is supported by funding from Wellcome and Cancer Research UK, and provides an exceptional and stimulating environment that promotes collaborative and interdisciplinary research in a supportive and modern setting, with access to state-of-the-art technologies such as super-resolution imaging, single-cell analyses, genome engineering, and genomics and computer modelling. Its postdoc association encourages scientific and social interactions and also provides career development and teaching opportunities.

Fixed-term: The funds for this post are available for 2 years in the first instance.

Click the 'Apply' button below to register an account with our recruitment system (if you have not already) and apply online.

Please quote reference PR39099 on your application and in any correspondence about this vacancy.

The University actively supports equality, diversity and inclusion and encourages applications from all sections of society.

The University has a responsibility to ensure that all employees are eligible to live and work in the UK.

The Ahringer laboratory at the Gurdon Institute in the University of Cambridge is seeking a talented and motivated Senior Bioinformatician to join their research group. Our research aims to decipher the step-by-step genomic regulation that drives developmental programmes.

A single-celled totipotent zygote produces a multitude of different cell types, however, the genome regulation that drives development is poorly understood. We address this by combining single-nucleus multi-omic profiling with the known lineage of C. elegans, which enables determination of the locus-specific regulation of chromatin and gene expression across all trajectories from the zygote to the differentiated state (http://www.ahringer.group.gurdon.cam.ac.uk/).

You will investigate genomic regulatory mechanisms in close collaboration with experimental colleagues, using existing cutting-edge software or devising new methods to analyse single-nucleus profiling data as well as other types of genomic and transcriptomic data. You will lead computational projects, participate in research activities of the laboratory as a whole, and contribute to the supervision of students, providing an ideal opportunity to develop an independent scientific career.

You will ideally have a strong background in bioinformatics and statistics and prior experience in the analysis single-cell and other types of high-throughput data (e.g., RNA-seq, ATAC-seq, ChIP-seq, CUT&TAG, and chromatin interaction). You should also have a PhD in a relevant subject, a sound understanding of molecular biology, and a strong publication track record in bioinformatics. You will be expected to be able to work independently, interact well in a dynamic multidisciplinary team environment, and be able to communicate ideas and results clearly.

The Gurdon Institute is a world-renowned centre of Developmental biology and Cancer research embedded in the University of Cambridge. It is supported by funding from the Wellcome Trust and Cancer Research UK, and provides an exceptional and stimulating environment that promotes collaborative and interdisciplinary research in a supportive and modern setting, with access to state-of-the-art technologies such as super-resolution imaging, single-cell analyses, genome engineering, and genomics and computer modelling. Its postdoc association encourages scientific and social interactions and also provides career development and teaching opportunities.

Limited funding: The funds for this post are available for 2 years in the first instance, with the possibility of extension subject to available funding.

Please ensure that you upload a covering letter and CV (including the names of two people who can provide a letter of reference) in the Upload section of the online application. The covering letter should outline your research interests and why you are interested in the post.

If you have any questions about this vacancy or the application process, please contact Arianna Pezzuolo at a.pezzuolo@gurdon@cam.ac.uk

Click the 'Apply' button below to register an account with our recruitment system (if you have not already) and apply online.

Please quote reference PR39094 on your application and in any correspondence about this vacancy.

The University actively supports equality, diversity and inclusion and encourages applications from all sections of society.

The University has a responsibility to ensure that all employees are eligible to live and work in the UK.

Applications are invited for a fully funded PhD studentship to investigate the mechanisms of apical domain formation in the Drosophila intestine under the supervision of Professor Daniel St Johnston. The studentship is part of the Horizon Europe Marie Sklodowska-Curie Doctoral Network (MSCA DN) "SurfEx": Epithelial Exchange Surfaces From organising principles to novel culture models of the gatekeepers of the body. The student will part of the SurfEx doctoral training network, which involves training and networking with other students at Universities across Europe. The project will be based in the Gurdon Institute, a leading institution in fundamental research on development and cancer, embedded in the first-class interdisciplinary environment of the University of Cambridge.

Project: The Drosophila adult midgut is a homeostatic tissue, in which cells constantly turn over and are replaced by the progeny of intestinal stem cells divisions. These progeny, called enteroblasts, are initially quiescent, lack an apical domain and lie on the basal side of the epithelium. In response to dying cells or signals that expand the gut, the enteroblasts integrate into the epithelium, polarise and form a new apical domain with a typical brush border. Two features of this process are very different from other epithelia in Drosophila. Firstly, enteroblast polarisation does not require any of the canonical epithelial polarity factors that have been identified in other tissues, and it depends instead on adhesion to the basement membrane, as is the case in mammalian epithelia (1). Secondly, a complete apical domain with brush border forms inside the epithelium before the enteroblasts reach the apical gut lumen, in a process that resembles lumen formation in mammalian epithelial cysts in 3D culture (2). The goal of the project is to identify the factors that initiate apical domain formation and to determine how these cooperate to direct the formation of the apical microvilli.

Objectives of the project include: · Perform a targeted RNAi screen for factors required for normal apical domain formation using the MARCM technique to express the RNAi in GFP labelled clones. · Analyse the phenotypes of the most interesting lines using an expansion microscopy protocol that we have developed for the Drosophila · Use CRISPR-mediated homologous recombination to insert fluorescent tags into the most promising candidate proteins and analyse their localisation in wild-type intestines and in mutants that affect apical domain formation. 1. Chen, J., Sayadian, A.-C., Lowe, N., Lovegrove, H.E., and St Johnston, D. (2018). An alternative mode of epithelial polarity in the Drosophila midgut. PLoS biology 16, e3000041. 10.1371/journal.pbio.3000041. 2. Chen, J., and St Johnston, D. (2022). De novo apical domain formation inside the Drosophila adult midgut epithelium. Elife 11, e76366. 10.7554/elife.76366 Funding: The studentship is supported by UKRI Horizon 2020 replacement funding and will be paid as pensionable salary. The monthly stipend after taxes, pension contribution and fees will be about £2,850 (depending on Euro/pound exchange rates) plus. Students will be responsible for their own visa fees etc.

Applicants should hold or be about to achieve a First or Upper-Second (2.i) class degree in a relevant biological science subject and ideally a postgraduate degree. Knowledge of cell biology and genetics and/or experience in Drosophila genetics and microscopy would be an asset. The post is a full-time appointment for 3 years and is open to applicants of any nationality. The mobility rules state that you must not have resided or carried out your main work or studies in the UK for more than 12 months in the 3 years immediately before the recruitment date.

Closing Date: The closing date for applications is 24th November 2023.

Interviews are expected to be held shortly thereafter.

The studentship will start between January and October 2024.

How to apply: Please send a covering letter that describes your previous research experience and motivation for the project, your CV with your University grades and the names and contact details of two academic referees who have agreed to act on your behalf to Prof Daniel St Johnston via email (ds139@cam.ac.uk). Applications for this studentship should be made to the Department of Genetics. The course code is BLGE22 https://www.postgraduate.study.cam.ac.uk/courses/directory/blgepdphg/apply

Please quote reference PR39047 on your application and in any correspondence about this vacancy.

The University actively supports equality, diversity and inclusion and encourages applications from all sections of society.

The University has a responsibility to ensure that all students are eligible to live and study in the UK.

We are looking for a highly motivated post-doctoral scientist to join the laboratory of Dr. Sumru Bayin at the Gurdon Institute, University of Cambridge. You will work in the Bayin Lab to explore the molecular mechanisms that regulate the regenerative potential of stem cells in the brain during development and in adulthood using various techniques including but not limited to single cell genomics, and in vivo and in vitro stem cell assays, organoid models and mouse genetics.

The Bayin Lab is interested in identifying the molecular mechanisms that regulate self-renewal, differentiation and plasticity of neural stem/progenitor populations during development and homeostasis, in order to discover how to stimulate repair of the brain upon injury. The cerebellum, which is a folded hindbrain structure that is important for skilled motor movements and higher order cognitive functions, has emerged as a powerful system to study the regenerative responses in the brain. We have previously shown that the cerebellum can recover from the loss of at least two types of neurons via distinct regenerative mechanisms (Wojcinski, Nature Neuroscience, 2017; Bayin, eLife, 2018; Bayin, Science Advances, 2021, Bayin and Joyner, Development, 2022). However, the full repertoire of molecular and cellular mechanisms that regulate neonatal cerebellar development and injury response remain to be studied.

Importantly, the regenerative potential of the neonatal cerebellum dramatically decreases once development ends, despite the presence of stem-like cells in the adult mouse cerebellum. This project involves using in vivo and in vitro approaches to identify mechanisms that control the developmental and regenerative responses of cerebellar progenitors in neonates and determine how it differs in adults in order to understand how we can facilitate efficient repair after injury to the brain. A variety of other projects on neural stem cell biology during brain development and pathologies are possible, depending on the candidate's interest and background.

Applicants must have (or expect to obtain) a PhD (or equivalent) in biological sciences, preferably in cell, developmental biology or in genetics. A background and/or interest in bioinformatics is desired. Importantly, we are looking for a highly motivated and enthusiastic team member who is a critical thinker and can work independently, and have excellent communication skills with the ability to work collaboratively within and outside of the laboratory, and promote positive research culture within the laboratory.

Our lab is funded by a Wellcome Career Development Award and the Royal Society and is a part of the vibrant research community at the University of Cambridge. Successful candidates will have access to career development activities and additional training opportunities offered by the School of Biological Sciences.

The salary range if appointed as a Research Associate is Grade 7 £36,024-£44,263 per annum, and the salary range if appointed as Research Assistant is Grade 5 £32,982 per annum with promotion to Research Associate on attainment of PhD.

Fixed-term: The funds for this post are available until 30 June 2025 in the first instance.

Click the 'Apply' button below to register an account with our recruitment system (if you have not already) and apply online.

Please quote reference PR38460 on your application and in any correspondence about this vacancy.

The University actively supports equality, diversity and inclusion and encourages applications from all sections of society.

The University has a responsibility to ensure that all employees are eligible to live and work in the UK.

We are seeking an enthusiastic Research Associate to study epithelial stem cell fate and tissue regeneration using a tissue engineering-type approach in a collaborative project led by Profs. Maria Alcolea (Cambridge Stem Cell Institute) and Benjamin Simons (Gurdon Institute).

The successful candidate will advance a multidisciplinary collaborative programme to i) reconstruct epithelial tissues ex vivo using a state-of-the-art long-term 3D Epithelioid culture method developed recently by Dr. Alcolea, and use this system to ii) study stem cell dynamics by combining fate mapping, live-imaging, and single-cell molecular profiling using quantitative methods pioneered by the Simons lab.

The aim will be to unveil the mechanisms governing epithelial stem cell behaviour in human and mouse with the long-term goal to develop strategies to improve tissue repair and prevent regenerative decay in ageing.

We welcome applications from candidates with experience in in vitro and/or in vivo experimental models, advanced image analysis, cellular/molecular biology, and interest in the epithelial stem cell field.

Alongside your core project, as a valued member of our team, you will be able to establish collaborative projects with other experimental scientists in the labs, as well as external collaborators. We are committed to supporting your career development and will provide mentoring and training opportunities to enhance your skills.

Applicants should have completed, or be close to completion of, a PhD in a relevant subject such as applied stem cell biology, development, 3D in vitro model systems, or cellular/molecular biology. The ideal candidate will show enthusiasm for epithelial biology, as well as a strong interest in underlying biological/disease processes. We are looking for a highly motivated individual capable of thinking and working independently, and as part of a dynamic and vibrant team.

Informal enquiries can be directed to Benjamin Simons (bds10@cam.ac.uk) and Maria Alcolea (mpa28@cam.ac.uk)

Fixed-term: The funds for this post are available for 3 years in the first instance.

Please ensure that you upload a covering letter and a CV in the Upload section of the online application. The covering letter should outline in brief your interest in the role and the skills that you would bring to the project. If you upload any additional documents that have not been requested, we will not be able to consider these as part of your application.

Please include details of up to three referees, including email address and phone number, one of which must be your most recent line manager.

The closing date for applications is: 8th October 2023.

The interview date for the role is: To be confirmed.

Click the 'Apply' button below to register an account with our recruitment system (if you have not already) and apply online.

Please quote reference PR38371 on your application and in any correspondence about this vacancy.

The University actively supports equality, diversity and inclusion and encourages applications from all sections of society.

The University has a responsibility to ensure that all employees are eligible to live and work in the UK.