Research Assistant

About Us

The role is that of a Research Assistant in Professor Andrew Tutt's laboratory within the Breast Cancer Now (BCN) Research Unit, based at the Innovation Hub, Guy's Cancer Centre, KCL Guy's Campus. Professor Tutt co-runs an additional laboratory with Professor Chris Lord at the Institute of Cancer Research. As such, the post-holder will be required to have an honorary contract at the ICR and will be required to work flexibly across the two sites; up to 50% of the appointee's time may be spent at ICR.

Professor Tutt's research group focuses on identifying and characterising novel biomarkers and targets for diagnosis and treatment of breast cancers, respectively. In particular, the group focuses on triple negative breast cancer (TNBC) and breast cancers associated with functional DNA damage repair deficiencies such as BRCA1 and BRCA2 mutations. In recent years, Professor Tutt and Lord's research group have recently published work in high impact journals including The New England Journal of Medicine, Annals of Oncology, Nature Medicine, Nature Genetics, Cancer Discovery, Nature Communications, Clinical Cancer Research and Oncogene.

As a Research Assistant, the post-holder will be required to provide high level technical support to the experimental work being undertaken in multiple projects within Professor Tutt's laboratories at both KCL and ICR sites. The post holder will be line managed by Professor Tutt, but may at times be supervised in specific areas by other members of Professor Tutt and Lord's ICR team including Dr Jennifer Trendell (Research Fellow), Dr Valeria Amodeo (Senior Scientific Officer) and Dr Stephen Pettitt (Senior Staff Scientist).The post holder will also work closely with, and in some instances work under the direction of other members of the KCL Breast Cancer Now Unit, including other BCN technical team members.

About The Role

The post holder's work will be focused on (but not limited to) working on the following main areas:

Processing of patient blood

As part of the BTBC study, led by Prof Tutt, we routinely collect blood from breast cancer patients at various timepoints in their treatment pathways. The post holder would be involved in processing blood for use in various projects within the laboratory. From most of these samples, we isolate plasma and immune cells/buffy coat. Plasma is subsequently used for isolation of circulating tumour DNA, which we primarily use for detection of the emergence of BRCA1/2 reversion mutations. From plasma we are also able to isolate extracellular vesicles for projects investigating blood derived biomarkers of breast cancer. Immune cells are used for isolation of germline DNA, co-culture experiments, FACs analysis and in vitro immune cell assays. In addition, whole blood is used for isolation of circulating tumour cells (CTCs) via Parsortix. The post-holder would be involved in processing/extraction of blood samples for all the applications detailed above.

Moreover, the post-holder will also be focused on various aspects of the bloods pipeline. This will include maintenance of the Parsortix equipment used for CTC isolation, optimizing the characterization of CTCs isolated from patient blood (this would include immunohistochemical analysis), use of the CellCelector platform, and generation of PDX and PDO models from CTC samples. The postholder will also be involved in projects focused on investigating biomarkers of breast cancer. This may also include isolation of extracellular vesicles (EVs) and characterizing their mRNA and protein cargo via various techniques.

Generation of PDO and PDX Models

To date, our team have successfully generated a large panel of both PDO and PDX models of breast cancer from patients' fresh cancer tissues which are subsequently used by the team as representative patient models for translational studies. The main aim of this work is to identify and characterise targets and associated biomarkers for development of novel breast cancer therapies and to investigate response to standard of care therapies with the aim of understanding mechanisms of therapy resistance. The post holder will be involved in establishing and characterizing both PDX and PDO models from patient tumour tissue or needle aspirate samples, patient liquid biopsies (such as pleural effusion and ascites samples) or CTCs isolated from patient bloods. As such the post holder must be prepared to perform both in vitro and invivo studies and will need to hold a Home Office Personal License.

PDO Work

The post holder will be involved in processing patient samples for PDO model generation, maintenance of 3D cell cultures, genetic perturbation of PDO models via siRNA and CRISPR/Cas9, and analysis of drug response. These experiments will require the post holder to be experienced in the use of echo liquid handler, microplate dispenser, incucyte, CellTiter-Glo and clonogenic survival cytotoxicity assays for performance of dose-response curves and synergy assays.

PDX Work

The post holder will be involved in processing patient samples for PDX model generation, health monitoring, monitoring of tumour growth and necropsy/ tumour dissection. In addition, the post holder may assist with the management of transgenic mouse colonies and drug dosing by multiple routes. As such, the post holder should be proficient in basic in vivo skills The post holder will also be involved in the characterisation of both PDX and PDO models - including DNA, RNA and protein extraction, STR profiling, preparation and submission of samples for sequencing and analysis of samples by qPCR, digital droplet PCR, simple western blot and automated capillary western blot (JESS). This will also entail coordination and interpretation of histology analysis and use of an automated slide scanner.

Preparation of patient and PDX/PDO samples for single cell sequencing

The post holder will lead on the preparation of samples for single cell sequencing projects. This will involve disaggregation of samples to single cells for storage, managing records of samples stores and coordinating shipment of samples to collaborator sites for single cell sequencing.

Providing technical support to various projects within the Tutt/Lord laboratories as required.

The post-holder will also provide expert support to Professor Tutt's laboratory, performing cell culture (2D + 3D), cell function and cytotoxicity assays and generating cell lines/ PDOs with knock down or overexpression of genes of interest (via siRNA or CRISPR/Cas9). The post holder will also be involved in performing protein assays including ELISA, simple western blot and automated capillary based western blot (JESS). For JESS in particular, the post-holder will be responsible for establishing and optimizing protocols for standard use. The post holder will also routinely perform RNA and DNA extraction, qPCR and digital droplet PCR, multi-colour flow cytometry, molecular cloning and microscopy acquisition and analysis. This will include confocal microscopy andmhigh content cell-based imaging (3i Advanced Spinning disk, ImageXpress, Opera Phoenix and tools for imaging quantifications). The successful candidate will also be responsible for the management of the Tutt team's Incucyte at KCL Guys Campus, providing training and coordinating servicing, maintenance and cost recovery.

In addition, the post-holder will be responsible for general laboratory maintenance, including preparation and maintenance of shared stocks and reagents, ordering consumables and reagents, management of equipment, participation in regular laboratory cleaning rota and maintenance of laboratory databases and inventories. They will be required to represent the Tutt KCL BCN Unit Project at ICR laboratory and departmental operational meetings and, where appropriate, should provide training on specialised laboratory skills to junior staff and students.

Key relationships

The post holder will be required to work in close collaboration with the Unit's translational research coordinators and clinical fellows, responsible for the acquisition of patient samples. Moreover, they will work closely with members of Professor Tutt's lab based at both KCL and ICR sites. They will also be expected to establish and maintain collaborative working relationships with members of the KCL based BCN team, led by Dr Sheeba Irshad and the wider Innovation Hub community. In addition, they will also work in close collaboration with ICR based Patient Derived Modelling teams who also focus on generation of PDX and PDO models; the post holder will play a key role in coordinating shipment of patient and PDX/PDO samples to the ICR to facilitate these programmes of work.

General Requirements

The candidate will be expected to take direct responsibility of specific research projects and will be required to be highly motivated and able to work independently. They will be required to provide original intellectual input and contribute to the design of experiments. They will drive the implementation and optimization of new techniques and be responsible for data analysis, generation of scientific figures and interpretation of results. They will be required to submit regular laboratory reports (currently bi-weekly) summarising their ongoing work, to be reviewed by senior team members. They will also be required to regularly present their work at internal lab meetings and to assist in the preparation of figures, legends and explanatory analysis and methodology text for manuscripts for the experimental work for which they have been involved.

The post holder will receive relevant supervision and training in specialised techniques and will meet with senior members of Professor Tutt's ICR based team on a regular basis to review results and plan experiments.

This position is 100% lab-based and requires daily on-site presence (Monday- Friday) during team core-working hours. The candidate will be required to work flexibly across our two laboratory sites: KCL Guys Campus and ICR; up to 50% of the appointee's time may be spent at ICR.

The post holder must be prepared to perform both in vitro and in vivo studies.

This is a full time post (35 hours per week), and you will be offered a fixed term contract for two years.

Research staff at King's are entitled to at least 10 days per year (pro-rata) for professional development. This entitlement, from the Concordat to Support the Career Development of Researchers , applies to Postdocs, Research Assistants, Research and Teaching Technicians, Teaching Fellows and AEP equivalent up to and including grade 7. Visit the Centre for Research Staff Development for more information.

About You

To be successful in this role, we are looking for candidates to have the following skills and experience:

Essential criteria

• BSC (Hons) degree or equivalent in a relevant subject. MSc awarded (or near completion) in a relevant subject is desirable. Extensive experience working in a research role within a target validation laboratory in the cancer field.
• Proven ability to work independently, to work under pressure to meet deadlines and to manage and prioritise own workload. Experience in the design, conduct, optimisation and analysis of experiments is essential. Able to demonstrate a comprehensive understanding of breast cancer patient subtypes, and the development of targeted therapies in particular those focused on DNA repair deficiencies.
• Highly experienced and competent at mammalian cell culture. Experience performing cell transfection, drug response experiments, cell-based functional assays and clonogenic survival cytotoxicity assays. Previous experience using liquid handling equipment (i.e. echo liquid handler and microplate dispenser) and use of live cell imaging (i.e. incucyte).
• Expertise in 3D organoid culture techniques, including experience in performing dose-response curves and synergy assays in organoid setting.
• Previous experience performing in vivo studies in the cancer setting in rodent models, performing tumour measurements and dissection/necropsy.
• Previous experience working with patient bloods to isolate plasma and buffy coat/immune cells. Previous experience with germline DNA and circulating tumour DNA isolation from blood.
• Highly experienced and competent in using protein assays (including ELISA, western blots and automated capillary based western blots). Highly experienced and competent in performing RNA and DNA extractions, PCR, qPCR and digital droplet PCR.
• Experience of genetic perturbation of cell lines and PDO models, including working with RNAi knockdown systems (including lentiviral work) and CRISPR/Cas9 editing.

Desirable criteria

• Co-authorship of at least 1 peer reviewed publication.
• Holds a UK Personal Licence for Home Office Modules A, B and C with previous experience working with tumour xenograft and PDX models. Expertise in various dosing techniques for delivery of cancer therapeutics in vivo including intraperitoneal injection (highest priority), oral gavage, IV injection. Experience of cell injections or surgery.
• Molecular Biology expertise including: DNA manipulation and subcloning
• Previous experience with extracellular vesicle isolation and circulating tumour cell isolation from bloods.
• Experience in multi-colour flow cytometry and microscopy acquisition and analysis. Including confocal microscopy and high content cell-based imaging (ie 3i Advanced Spinning disk, ImageXpress, Opera Phoenix and tools for imaging quantifications).

Downloading a copy of our Job Description

Full details of the role and the skills, knowledge and experience required can be found in the Job Description document, provided at the bottom of the page. This document will provide information of what criteria will be assessed at each stage of the recruitment process.

Further Information

We pride ourselves on being inclusive and welcoming. We embrace diversity and want everyone to feel that they belong and are connected to others in our community.

We are committed to working with our staff and unions on these and other issues, to continue to support our people and to develop a diverse and inclusive culture at King's.

As part of this commitment to equality, diversity and inclusion and through this appointment process, it is our aim to develop candidate pools that include applicants from all backgrounds and communities.

We ask all candidates to submit a copy of their CV, and a supporting statement, detailing how they meet the essential criteria listed in the person specification section of the job description. If we receive a strong field of candidates, we may use the desirable criteria to choose our final shortlist, so please include your evidence against these where possible. To find out how our managers will review your application, please take a look at our ' How we Recruit ' pages.

Interviews are due to be held at the start of February, exact date TBC.

This post is subject to Disclosure and Barring Service and Occupational Health clearances.