RETORNA proposes breakthrough research, distributed in 10 individual projects, performed by 10 Doctoral candidates in the following countries: Ireland, Spain, Netherlands, Türkiye, Germany, and Italy.
DC4 and DC8 will be hired by UNIVERSIDAD DE ALICANTE (UA) and work mainly in the lab in Alicante, with various secondments in the RETORNA consortium.
2 Doctoral Candidate positions (DC4 and DC8) at UNIVERSIDAD DE ALICANTE (UA) are available in the framework of the Marie Skłodowska Curie – Doctoral Networks (MSCA-DN) project “Targeting RNA as an approach for treating retinal disease” (RETORNA).
RETORNA network summary description:
RETORNA aims to treat retinal diseases (RD) by using RNA therapy. Among the research objectives, we will study different types of RNA that are expressed in retinal cells. By observing bioinformatic models, cell and tissue cultures, animal models, and human patients, we will be able to create RNA profiles for different RD. This screening will identify several targets that will be used as therapeutic approaches. Then, selected RNAs will be used to treat different RD, such as macular degeneration and retinitis pigmentosa.
The proposed doctoral network (DN) will provide an innovative, international, multi/interdisciplinary platform to train young scientists in the field of vision science.
For more information about RETORNA: https://cordis.europa.eu/project/id/101073316
Get to know the lab:
Our lab focuses on the study of the morphology and physiology of the vertebrate retina in healthy and pathological conditions, using mice models and human tissue. We are especially interested in the study of the retinal remodeling that occurs during neurodegenerative diseases such as retinitis pigmentosa or central areolar choroidal dystrophy and in the search for possible therapies to prevent, reverse, or slow retinal degeneration. For that, we use a wide variety of techniques to assess retinal histology (immunohistochemistry, confocal microscopy, electron transmission microscopy), visual behavioral (optomotor test), and electrophysiological response (electroretinogram), or molecular biology (western blot, qPCR).
For more information about the research group: Neurobiología del sistema visual y terapia de enfermedades neurodegenerativas (NEUROVIS)
Details of the individual project DC4:
Title of the DC4 project: Study of microRNA expression profile in Central Areolar Choroidal Dystrophy. A translational study using a new CRISPR-generated animal model
Host supervisor: Dr. Natalia Martínez (UNIVERSIDAD DE ALICANTE, Spain)
Objectives: Central Areolar Choroidal Dystrophy (CACD) is a monogenic hereditary retinal dystrophy that involves progressive retinal degeneration. It usually causes a gradual loss of visual acuity between 30 and 60 years old, and color perception impairments. In most cases, CACD presents an autosomal dominant inheritance pattern in which patients carry a single mutation in the peripherin gene (PRPH2 or RDS, Retinal Degeneration Slow), although other genes may be involved in some individuals. Peripherin is a glycoprotein essential for generating and maintaining the photoreceptor outer segment disks where retinal phototransduction takes place. Five different mutations in peripherin have been histologically and functionally described as causing this disease and this project will focus on the p.Arg195Leu mutation which was first described in a carrier family in Japan and later in German and Spanish families. In Spain, CACD has been diagnosed in a large family from the Iguña Valley, Cantabria. The existence of this family, with a large number of members affected with the same mutation, is a unique opportunity to in-depth study the CACD pathology in a homogeneous population. Thus, our new CRISPR-generated animal model (Prph2 KI/WT mouse), which reproduces the same pathological characteristics as CACD patients, will allow a better description of the disease and increase the current knowledge about it.
Approach: We will study for the first time the total microRNA expression profile in the retina of Prph2 KI/WT mouse, particularly focusing on the miRNAs which have an important role in the maintenance and function of photoreceptor outer segments (e.g miR-183/96/182 cluster) and also on those miRNAs associated with inflammatory pathways (e.g. miR-155 and miR-124). In addition, a study of retinal morphology and physiology will be carried out to describe the neuropathological events that occur in CACD patients and in this new mouse model carrying the same mutation. This study will allow testing of new neuroprotective therapies using RNA-based strategies in Prph2 KI/WT mice, as a first approach for translational medicine.
Expected Results: 1) Analysis of retinal morphology and physiology to describe the neuropathological events that occur in CACD patients and in this new mouse model carrying the same mutation. 3) Assessment of the global expression profile of mRNAs and miRNAs in Prph2 KI/WT mouse across the progression of the retinal neurodegenerative process. To establish a correlation between the miR-183/96/182 cluster and their relationship with peripherin mutation. 3) In silico identification of key pathways regulated by the RNAs and miRNAs that are modified by the peripherin mutation and specifically miR-155 and miR-124. 4) Design and evaluation of a possible therapy for CACD using RNA-based strategies in Prph2 KI/WT mice.
Secondments are foreseen during the 36 months project.More information about DC4: 1 funded PhD – study of microRNA expression profile in Central Areolar Chroidal Dystrophy | EURAXESS (europa.eu): RETORNA
Details of the individual project DC8:
Title of the DC8 project: CRISPR therapy in retinal hereditary dystrophy. A translational study using an animal model and retinal organotypic cultures.
Host supervisor: Dr. Nicolás Cuenca (UNIVERSIDAD DE ALICANTE, Spain)
Objectives: The use of the CRISPR system as a gene editing tool is currently one of the strategies in which more efforts are being invested for the treatment of retinal hereditary dystrophies. The main objective of this project is to develop a new therapeutic approach for a Central Areolar Choroidal Dystrophy (CACD) mouse model (Prph2 KI/WT) using the leading technology of CRISPR.
Approach: For that, sgRNA for the mutated allele will be designed. Plasmids containing sgRNAs and the high-fidelity cas9 under a cone and rod promoter derived from the human rhodopsin kinase gene will be used. First, skin fibroblast from Prph2 KI/WT mice will be obtained and maintained in in vitro cultures. After, they will be transfected with the CRISPR system using the lipofectamine method. The mutated allele will be recognized by sgRNA and induce a cut in this region. The non-homologous end joining (NHEJ) system will rejoin the strand adding small inserts and deletions (indels) and interrupting the mutated sequence. As the mutation of interest is dominant, its ablation by CRISPR would be enough for therapy, maintaining the peripherin expression in the non-mutated allele. After that, the efficiency of the CRISPR-mediated therapy for the re-establishment of the wild-type phenotype will be analyzed in retinal organotypic cultures from Prph2 KI/WT mice. Finally, once the efficiency of the CRISPR system has been tested in fibroblasts and retinal organotypic cultures, in vivo treatments will be done to assess the efficacy and safety of the treatment in a living organism. Functional state of the retina at different ages will be assessed by ERG and optomotor test and retinal structure and morphology will be determined by OCT, immunohistochemistry, confocal microscopy, and transmission electron microscopy.
Expected Results: Novel gene editing approaches based on the CRISPR-Cas system will be designed and tested in vitro. In vivo validation of the results will be carried out in an animal model. Specifically, the expected results include 1) evaluation of the efficiency of the designed CRISPR tools in the editing of the mutated sequence using Prph2 KI/WT mice fibroblasts in in vitro cultures. 2) Determination of the efficiency of CRISPR-mediated therapy for the reestablishment of the wild-type phenotype in retinal organotypic cultures from Prph2 KI/WT mice. 3) Evaluation of the efficiency of CRISPR therapy to prevent retinal degeneration.
Secondments are foreseen during the 36 months project.
For more information about DC8: 1 funded PhD – study of CRISPR therapy in a retinal hereditary dystrophy | EURAXESS (europa.eu)
Master Degree or equivalent
Candidate researchers must:
- have MSc level training in Biological Sciences, Biotechnology, Neurosciences, Biomedicine, or any other field that matches the DC4 and/or DC8 projects.
- possess scientific skills for the project and research experience.
- possess a good working level of English: candidates must demonstrate during the interview a good ability to understand and express themselves in both written and spoken English, sufficiently high to fully benefit from the experience.
- be highly motivated.
- be creative and possess a high level of independence.
Other desired skills for DC4:
1. Good experience with animal handling.
2. Basic knowledge of bioinformatic tools for RNA data analysis.
Other desired skills for DC8:
1. Cell culture experience
2. Basic experience or good theoretical knowledge of CRISPR-Cas systems and/or other gene editing technologies.
RETORNA Doctoral candidates DC4 and DC8 will be employed according to the rules for Doctoral Candidates in MSCA Doctoral Network and the general regulations of the hosting institution.
The monthly financial package will include the following researcher allowances:
1) Living allowance
2) Mobility allowance
3) Family allowance if applicable.
The full-time gross yearly salary amounts to € 36.026,00 Euro (family allowance will be calculated only if applicable).
The guaranteed PhD funding is for 36 months starting from autumn 2023.
The selected candidate, together with other 9 DCs that will be selected, will benefit from a large variety of activities foreseen for them. DCs at RETORNA will be provided with unique multi-disciplinary and multi-sectoral training. First and foremost, DCs will be trained as scientists, each of them in their host institution, at their research secondments, and through local and network-wide events. Next, thanks to the partnership between academic and non-academic entities, DCs will receive multi-sectoral inputs from both worlds. This will happen via lectures and workshops in our varied training program.
Please read carefully ALL the eligibility criteria and apply only if you possess them:
- candidates can be of any nationality
- must comply with the following mobility rule: researchers are required to undertake trans-national mobility (i.e., move from one country to another) and participate in all the activities foreseen by the project when taking up the appointment (trainings, summer courses, annual meetings, lectures, participation in conferences, public activities).
- possess a Master degree or an equivalent that allows the access to the doctoral program in the Universidad de Alicante
- be, at the date of recruitment, a doctoral candidate (i.e. not already in possession of a doctoral degree). Researchers who have successfully defended their doctoral thesis but who have not yet formally been awarded the doctoral degree will not be considered eligible.
- not have resided or carried out their main activity (work, studies, etc.) in Spain for more than 12 months in the 3 years immediately before the recruitment date. Short stays, such as holidays, are not taken into account.
The RETORNA selection procedure is open, transparent, merit-based and in line with the Code of Conduct for the Recruitment of Researchers and the European Charter for Researchers.
The criteria for recruitment of DCs will respect the principles of non-discrimination contained in The Charter of Fundamental Rights of the European Union.
It is the policy of the RETORNA project to promote and give equal opportunities regardless of gender and stimulate gender balance.
Interested candidates should submit the following documents via email to email@example.com, indicating in the e-mail title «RETORNA – DC4 or DC8 application»:
- a detailed CV, including – if applicable – relevant publications
- a motivation letter, indicating why you wish to conduct this research project
- two references
- transcripts of bachelor and master degrees
- English certificate if any.
All documents must be named as «type of document_NameSurname» (i.e. Motivation letter_Andreea Craciun»)
We encourage candidates to send any other certificates, representative publications, academic references, or links demonstrating their experience and interest in the project.
The selection process will foresee the following steps:
1. Eligibility: the RETORNA recruitment committee will check that each application is complete and that applicants fulfill the eligibility criteria described in the previous section.
2. Evaluation: each eligible application will be assessed by the principal investigators of our network. The principal investigator will select up to four candidates per position for the following steps:
a. Online interviews: online interviews will be scheduled, in-person interview will be organized where possible. Short-listed candidates will be invited for an online interview with the supervisor responsible for the research project. At least one member of the recruitment committee will attend the online interviews.
b. Selection results: our recruitment committee will notify short-listed candidates of the results.
c. Hiring process and enrollment: the selected candidates will be put in touch with the principal investigator and the HR Department of the Universidad de Alicante to initiate the hiring procedure.
Applicants who have not been successful but who have received a positive evaluation will be put on a waiting list to cover possible withdrawals and future positions.
- Deadline for applications: 24th of May
- Eligibility and Evaluation: 25-26th of May 2023
- Online Interviews: 29th May – 6th June 2023
- Notification to candidates: 7th of June 2023
- Hiring process: June – August 2023
- Start date of the PhD: September – October 2023
Company/Institute: Universidad de Alicante
State/Province: Comunidad Valenciana
Postal Code: 03690
Street: San Vicente del Raspeig s/n