RESISTANCE TO HYPOXIA IN RAINBOW TROUT: DECODING THE ROLE OF CHAPERONEMEDIATED AUTOPHAGY
Contact
Iban SEILIEZ 05.59.51.59.99 iban.seiliez@inrae.fr
Offer details
PhD Supervisor: Iban SEILIEZ (Research Director, iban.seiliez@inrae.fr)
Host laboratory: UMR1419 INRAE/UPPA NuMeA, St Pée-sur-Nivelle, France
Starting Date: 01/10/2025
Duration: 36 months
Gross Monthly Salary: 2200 €
Funding: ½ University of Pau + ½ INRAE
Application Deadline: June 1st, 2025
OFFER DESCRIPTION
During the last 60 years, the global population has increased with an annual rate of 1.6%, and is
predicted to reach 9.7 billion by 2050 according to the Food and Agriculture Organization (FAO) of the
United Nations (UN)1. Hence, providing a sustainable food supply to that exponentially growing human
population is one of the core challenges of the Sustainable Development Goals of the 2030 UN Agenda.
Aquaculture will definitely play an important role in fulfilling that goal. Factually, fish farming
production already reached 56% of fish consumed in 2020, and still has the potential to steadily
increase in the long term1. However, despite the considerable promise of global aquaculture, the
sector’s sustainability hangs in the balance, as the predicted effects of climate change are not merely
a future concern but an immediate reality2. Aquaculture farms are thus already facing challenges such
as rising water temperatures, acidification, and hypoxia, highlighting the urgent need for innovative
solutions to ensure sustainable production in this changing environment. In this context, studying and
harnessing the mechanisms and processes of cellular resilience, which integrate environmental
stress signals and enable organisms to adapt, is of particular importance, in order to increase the
robustness of fish and thus guarantee more stable and predictable production.
Among the mechanisms of cellular resilience, chaperone-mediated autophagy (CMA) attracted
the attention of many scholars in recent years3. CMA is a major pathway of lysosomal proteolysis4. In
detail, during CMA, cytosolic proteins containing a pentapeptide sequence biochemically similar to
KFERQ (lysine-phenylalanine-glutamate-arginine-glutamine) are first recognized by the heat-shock
protein HSC70. The substrate-chaperone complex then docks at the lysosomal membrane through
specific binding to the cytosolic tail of the protein LAMP2A, the only one of the three spliced isoforms
of the LAMP2 gene recognized to be essential and limiting for CMA activity. LAMP2A then organizes
into a multimeric complex that allows substrates to translocate across the lysosomal membrane,
where degradation by acid hydrolases occurs. Besides being involved in protein quality control(s)
(resulting from its ability to selectively target damaged or non-functional proteins for degradation),
the diversity of the sub-proteome degraded by CMA links this function to the regulation of a variety of
intracellular processes including the control of transcription, cell cycle and cellular energetics, among
other key cellular processes3, 4. Recently, CMA has been recognized as a critical mechanism for cell
survival under hypoxic stress in various models5-7. While the exact mechanisms underlying this effect
remain to be clarified, these findings underscore the promising potential of CMA activation as a
protective strategy in low oxygen conditions.
In fish, the existence of CMA has been overlooked until recently. Indeed, the lack of any
identifiable LAMP2A protein outside of the tetrapod clade led many authors to consider this function
to be restricted to mammals and birds8. However, we recently shed new light on the evolutionary
history of LAMP2A and demonstrated its expression in most of the fish investigated, suggesting that
CMA likely appeared earlier during evolution than initially thought9. In this regard, we recently
provided evidence for a functional CMA process in rainbow trout (RT, Oncorhynchus mykiss) and
showed that, akin to mammals, CMA also plays a key role as a gatekeeper of cellular homeostasis in
this species10, 11. However, our understanding of the CMA function in RT is still fragmentary, and many
questions remain unanswered, notably regarding its regulation and physiological roles in this species.
In this context, the present PhD project aims to bridge basic and translational research by
investigating CMA in RT under hypoxic stress and exploring its potential to mitigate the detrimental
effects of hypoxia. The expected results will deepen our understanding of CMA and determine the
importance of this cellular stress response pathway in developing new farming strategies that ensure
sustainable aquaculture production in the context of global changes.
References (those from the hosting lab are in bold)
1. FAO. 2024. The State of World Fisheries and Aquaculture 2024 – Blue Transformation in action.
Rome.
2. Yadav et al. Climate change effects on aquaculture production and its sustainable management
through climate-resilient adaptation strategies: a review. Environ Sci Pollut Res. 2024, 31, 31731–
31751.
3. Valdor and Martinez-Vicente M. The Role of Chaperone-Mediated Autophagy in Tissue
Homeostasis and Disease Pathogenesis. Biomedicines. 2024, 12(2):257.
4. Kaushik S, Cuervo AM. The coming of age of chaperone-mediated autophagy. Nat Rev Mol Cell
Biol. 2018 Jun;19(6):365-381.
5. Ghosh et al. Chaperone-mediated autophagy protects cardiomyocytes against hypoxic-cell death.
Am J Physiol Cell Physiol. 2022 323(5):C1555-C1575.
6. Kshitiz, et al. Lactate-dependent chaperone-mediated autophagy induces oscillatory HIF-1α
activity promoting proliferation of hypoxic cells. Cell Syst. 2022, 13(12):1048-1064.e7.
7. Dohi et al. Hypoxic stress activates chaperone-mediated autophagy and modulates neuronal cell
survival. Neurochem Int. 2012, 60(4):431-42.
8. Galluzzi et al. Molecular definitions of autophagy and related processes. EMBO J. 2017,
36(13):1811-1836.
9. Lescat et al. Chaperone-Mediated Autophagy in the Light of Evolution: Insight from Fish. Mol
Biol Evol. 2020, 37(10):2887-2899.
10. Vélez et al. Chaperone-mediated autophagy protects against hyperglycemic stress. Autophagy.
2024 Apr;20(4):752-768.
11. Schnebert et al. Chaperone-Mediated Autophagy in Fish: A Key Function Amid a Changing
Environment. Autophagy Reports.
WORKING ENVIRONMENT
Nutrition Metabolism Aquaculture (NuMeA) INRAE-UPPA research unit is known worldwide and
stands as a leading French research structure devoted to all aspects of fish nutrition and metabolism,
including protein, lipid and carbohydrate metabolism, energetics, and environmental impact. Research
at NuMeA is driven by the challenges posed by limited marine resources, the global expansion of
aquaculture, and the ongoing effects of climate change. The unit focuses on understanding the cellular
and molecular mechanisms, particularly nutrient-driven processes, that regulate key metabolic
functions and growth in fish. Ultimately, the goal is to provide innovative aquaculture strategies that
ensure the production of healthy, nutritious food for the global population while promoting
sustainability and animal welfare.
In this context, the research initiative led by Iban Seiliez seeks to advance our understanding of
the regulation of autophagy and its pivotal role in maintaining cellular metabolism and homeostasis in
fish. Autophagy, a highly conserved process across evolution, acts as a key mechanism of cellular
resilience, integrating environmental stress signals and enabling organisms to adapt effectively. Given
the increasing environmental stresses faced by aquatic species, investigating autophagy responses is
essential for identifying breeding strategies that enhance the robustness of fish and ensure more
stable, predictable aquaculture production. To achieve our research objectives, we adopt a
comprehensive, multifaceted approach that combines both in vivo and in vitro methodologies. This is
further supported by state-of-the-art technologies such as super-resolution fluorescence imaging,
CRISPR-Cas9 gene editing, siRNA-mediated gene knockdown, and advanced proteomics analyses.
These cutting-edge tools allow us to investigate the intricate mechanisms of autophagy in
unprecedented detail, providing valuable insights into how fish can be made more resilient to
environmental stressors, ultimately contributing to the development of more sustainable and efficient
aquaculture practices.
QUALIFICATIONS
The position requires a master degree (or equivalent) in biology, biotechnology, life sciences, or related
overlapping fields.
Mandatory qualifications:
o Solid foundations in molecular and cellular biology
o Good written and verbal communication skills in English and ability to work in an
international environment
Expected qualifications:
o Self-motivation, independence, and enthusiasm
o Excellent work ethic and commitment to the job
o Strong problem-solving skills and attention to detail
o Ability to work collaboratively in a multidisciplinary team
o Flexibility and adaptability to changing research environments
APPLICATION
Your application must include:
Cover letter explaining:
o why the candidate considers oneself suitable for the position
o what motivates the candidate to apply for the position and what the candidate expects from
this position
CV
Diploma for bachelor’s and master’s degree
Transcript of grades/academic record for bachelor’s and master’s degree
Documentation of English proficiency
At least 2 references with contact information
Master’s thesis, and any other academic works (English or English translation)
Qualification with a master’s degree is required before commencement in the position. If you are near
completion of your master’s degree, you may still apply and submit a draft version of the thesis and a
statement from your supervisor or institution indicating when the degree will be obtained. You must
still submit your transcript of grades for the master’s degree with your application.
ASSESSMENT
The applicants will be assessed by an expert committee. The committee’s mandate is to undertake an
assessment of the applicants’ qualifications based on the written material presented by the applicants.
The applicants who are assessed as best qualified will be called to an interview. The interview should
among other things, aim to clarify the applicant’s motivation and personal suitability for the position.
WHERE AND WHEN TO APPLY
The complete set of documents listed above must be submitted to iban.seiliez@inrae.fr by June 1st,
2025. Applications submitted after this date will not be considered. Incomplete applications will be
deemed ineligible and will not be evaluated.
CONTACT
iban.seiliez@inrae.fr
+33 5 59 51 59 99