Project title	Understanding the non-ciliary retinal function of BBSome in Drosophila model
Grant code	PN-IV-P2-2.1-TE-2023-0123
Contract no.	59TE/08.01.2025
Project director	Levente KOVACS, PhD, assistant professor, BBU
Funding volume	483.924  RON
Funding periode	2025-2026 (24 months)

Project Summary
Blindness and progressive vision loss remain poorly understood in many genetic disorders, and the situation is even more complex in Bardet–Biedl syndrome (BBS). The genes implicated in this syndrome encode subunits of the BBSome, an evolutionarily conserved protein complex involved in the formation of cellular structures known as cilia, but which may also have non-ciliary functions. The aim of this project is to distinguish the ciliary and non-ciliary roles of the BBSome in photoreceptors, using Drosophila as a model organism.

The strengths of this proposal include:

1. The use of a well-characterized model organism with clearly distinct ciliated and non-ciliated cell types.
2. Promising preliminary data suggesting a non-ciliary function of the BBSome in the Drosophila retina.
3. A diverse set of approaches to characterize the genetic, biochemical, and cellular aspects of the BBS model.

Our team will consist of motivated early-career researchers, and the project will be highly collaborative, with well-defined roles that will support the professional development of these young scientists. The project leader has extensive experience in collaborative research, has contributed to the establishment of several new Drosophila laboratories, and possesses strong expertise with the techniques proposed here.

We anticipate that our work will lead to significant discoveries, which we intend to publish in leading scientific journals and present at scientific conferences, while also ensuring that the results are accessible to the general public.

Nominated team members
– dr. Levente KOVACS, project coordinator
– dr. Sarolta SZENTES, postdoctoral member
-dr. Alexandru Vlad TOMA, postdoctoral member

Related publications:
– Golgi Functions of Drosophila Gorab are Required in the Male Accessory Gland to Elicit Post-Copulatory Behavior of the Female. Levente Kovacs, Mark S Ladinsky, David M. Glover (in revision)

Reporting Phase I – jan-dec, 2025
Main results:

• generation of CRISPR/Cas9 mutant line collection
• generation of transgenic line collection expression fluorescent reporters
• phenotypic information linked to retina function by phisiological tests
• detailed mechanistic information by phase contrast, fluorescent and transmission electron microscopy
• information about the localization of BBSome subunits by fluorescent imaging of trangenic lines
• identification and listing the potential interacting partners in retina by pull-down and mass spectrometry
  

Cognitive and Socio-Economic Impacts

1. Advancing fundamental knowledge on the mechanisms of rare diseases

The project contributes to a better understanding of Bardet–Biedl syndrome, a rare genetic disorder, by identifying non-ciliary functions of the BBSome complex in vision and metabolism. These findings reshape the scientific community’s perspective on the roles of this complex, creating the foundation for new research directions and innovative therapeutic approaches.

2. Strengthening national expertise in molecular biology and genetics

The generation of new mutant and transgenic lines, together with the implementation of cutting-edge methodologies, enhances Romania’s research capacity. The project develops advanced competencies in genetic editing, biochemical analysis, and imaging, supporting the growth of human capital and attracting resources to the life sciences sector.

3. Increasing innovation potential in the health sector

By elucidating a fundamental mechanism involved in visual degeneration, the project may indirectly contribute to identifying new therapeutic targets for retinopathies and metabolic diseases. This knowledge has potential for transfer to biotechnology, ophthalmology, and metabolic research, fostering interdisciplinary collaborations and possible clinical applications.

4. Socio-economic impact through the development of a relevant experimental model

Establishing Drosophila as a valid model for studying certain manifestations of Bardet–Biedl syndrome reduces the cost of biomedical research by replacing more expensive animal models while accelerating the generation of results. The scientific community thus gains access to an affordable, reproducible, and ethical model that supports rare disease research at the international level.

5. Increasing scientific visibility and international collaborations

The project involved interactions with renowned laboratories abroad and generated results with strong potential for publication in international journals. This contributes to strengthening Romania’s position in European research networks, attracting new collaboration opportunities, and fostering researcher mobility and investment in the biomedical field.