Photocontrol of cell adhesion mechanism

The project has started on 01.06.2021 and the operative plan has been discussed with the head of Biotechnology group which host the project.

The experimental activity continued with the design of bioinspired surfaces and the definition of criteria for the selection of the best experimental approach.

The training activity within WP1 led the principal investigator to complete the “Antimicrobial resistance” course organized by the Technical University of Denmark (DTU) and offered through Coursera (online course provider).

Publication in peer-reviewed international journal SN Comprehensive Clinical Medicine: International Scientific Collaboration Is Needed to Bridge Science to Society: USERN2020 Consensus Statement | SpringerLink

Publication date 01.09.2021.

The project activity continues with the design of biohybrid materials and photoswitchable compounds to modulate cell-cell adhesion. Regarding the development of photoswitchable drugs, the principal investigator signed a collaboration research agreement N 1.1.-5/28 with the Institute of Bioengineering of Catalonia, Barcelona (Spain) to carry out photopharmacological research in their facilities.

As part of the training activity planned in WP2, the principal investigator attended the Summer School on Drug Design (online mode) 13-17 September 2021 at the University of Vienna, focusing on pharmacoinformatics. As results of attendance to the school and poster presentation the principal investigator received 4 ECTS from the University of Vienna and expanded her competences on virtual screening and docking analysis.

The principal investigator delivered a poster presentation at the “EUROPIN Summer school on Drug Design- SSDD21 13-17 September 2021 (Online) titled: “Design of photoswitchable acetylcholinesterase inhibitors” and an invited talk at the USERN International Congress (online – Organized by Universal Scientific Education and Research Network (USERN)), 06-13 November 2021 titled “Biohybrid electrospun materials: the role of complex interfaces”(08.11.2021).

Publication date 30.11.2021.

On the 21^st of February a review paper discussing, among other things, the field of photocontrol of protein-protein interactions in microtubule formation through photopharmacology has been accepted for publication in Frontiers in Molecular Bioscience. Susanna Eli*, Rossella Castagna*, Marina Mapelli, Emilio Parisini – “Recent approaches to the identification of novel microtubule-targeting agents” (DOI: 10.3389/fmolb.2022.841777)

*shared first authorship

Training activities have been followed on Circular Dichroism spectroscopy from Jasco company and Isothermal Titration Calorimetry (ITC) from Malvern company in the framework of the training activities on biophysical techniques (WP4).

Project PI attended the training course “Horizon Europe: Quick guide to tackle gender dimension and cross-cutting issues – Expert Insights” held by EMDESK Academy (10 February, 2022 Online).

Dissemination 11.02.2022: Project PI was a speaker for the International Day of Women in Science (11th February 2022) at a communication event organized by the Barcelona Institute of Science and Technology (BIST) delivering a talk on scientific activity and virtual guided lab tours targeting school students. (Online – Escola Gaspar, Barcelona – Spain).

Publication date 28.02.2022.

The experimental activity continued in the production and purification of the cell-adhesion proteins that will be used in the crystallization and ligand binding experiments. From the study of the structural characteristics of cell adhesion inhibitory molecules, suitable fragments have been identified for their engineering for the development of light-sensitive analogs. The synthesis of those light-sensitive compounds is currently underway.

On the 30^th of March a review paper “Recent approaches to the identification of novel microtubule-targeting agents” has been published in Frontiers in Molecular Biosciences (9:841777 doi: 10.3389/fmolb.2022.841777) Susanna Eli, Rossella Castagna, Marina Mapelli, Emilio Parisini.

On the 4^th of May, a project proposal has been submitted for the call Horizon Europe Pathfinder Open (Call: HORIZON-EIC-2022-PATHFINDEROPEN-01). Dr. Rossella Castagna is Head of Partner (LIOS) unit.

Dr. Rossella Castagna followed the webinar on IP in EU funded projects with a special focus on MSCA held by the European IP Helpdesk – on April 13th 2022.

Dr. Rossella Castagna completed the course “Master on EU Projects Design & Management 2021-2027” held by Europa Business School (Amsterdam) for a total of 40h lessons from January 2022 to May 2022.

Publication date 31.05.2022.

The scientific activity continued with the design and synthesis of photoswitchable compounds, as well as with their characterization. The design of photochromic analogues based on an azologization approach led to the definition of a successful synthetic route and a small library of compounds that are currently under investigation. The design has been conducted based on the results of virtual screening and docking experiments conducted previously.

Training activities

Dr. Castagna attended the workshop on “Molecular dynamics simulation with GROMACS” held at the LIOS by Dr. Nikhil Agrawal (June 27th – July 1st 2022).

Seminar

Dr. Castagna gave a seminar at the LIOS on “Electrospinning technique and applications” on the potentiality of the electrospinning technique to produce functional surfaces. June 13^th 2022.

Conference presentation

Dr. Castagna attended the FEBS3+ Conference of the Estonian, Latvian and Lithuanian Biochemical Societies, organized by the Estonian Biochemical Society, Tallin (Estonia) 15-17 June 2022. At the conference, Dr. Castagna presented a poster on photopharmacology titled “Photoswitchable ligands as tools to modulate biological activity”.

International collaborations

A successful collaboration has been established with Prof. Elena Ishow from Nantes University (France) on the development of functional materials towards the removal of bacteria from water. The collaboration has led to a joint bilateral grant application between LIOS and Nantes University. Details are as follows: Project submitted for Latvian-French Hubert Curien partnership programme OSMOZE 2022. Bilateral project France (Nantes University – Prof. Elena Ishow) and Latvia (LIOS – Dr. Rossella Castagna).  Submitted on June 3^rd 2022

Publications involving PhOAMS’s PI

• A review paper describing the role of photopharmacology in animal behavior control has been published in the Journal of Molecular Neuroscience. Castagna R. et al. Orthogonal control of neuronal circuits and behavior using photopharmacology”.  J. Mol. Neurosci. 2022, 72, 1433–1442. https://doi.org/10.1007/s12031-022-02037-3 (Springer Nature, I.F. 3.4)
• An original research paper on a new class of photoswitchable compounds applied for the first time in photopharmacology has been published in the Journal of American Chemical Society.  Castagna R. et al. Donor–Acceptor Stenhouse Adduct Displaying Reversible Photoswitching in Water and Neuronal Activity. J. Am. Chem. Soc. 2022, 144, 34, 15595–15602. DOI: 10.1021/jacs.2c04920 (ACS, I.F. 16.3)

Publication date 31.08.2022.

PhOAMs scientific activity continued with the purification and the functional characterization of those photoswitchable compounds synthesized so far. This was done in order to assess their photochemical properties. Moreover, the activity on functional surfaces continued with the production of functional mats by means of the electrospinning technique.

A first secondment visit at the Aix-Marseille University in the group of Prof. Frederic Andrè has been organized for the beginning of December 2022. During this stay, the small library of photoswitchable compounds will be tested in cell-cell adhesion assays.

Training activities

• Dr. Castagna attended the INSERM workshop on “Photopharmacology: control of protein using synthetic photoswitches” held in Bordeaux 21-23 November 2022.
• Dr. Castagna attended the 1 week course on “Biomolecular Modelling” at LIOS (5-9 September 2022). The course was held by Prof. Alfonso Gautieri (Politecnico di Milano, Italy) with 5 theoretical lectures and 5 hands-on sessions.

Invited Seminar

Dr. Castagna was invited by Prof. Elena Ishow to deliver a seminar at Nantes University (Nantes, France) titled “Electrospun nanofibers: a room for improvement for functional materials applications” on 25th November 2022.

Conference presentation

• Dr. Castagna delivered an invited talk at the 2nd LIOS Conference (Riga, Latvia) titled “Electrospun fibers for smart-materials interfaces” on 28th November 2022.
• Dr. Castagna delivered (online) an invited talk at the international USERN2022 Conference “Looking at Universe, Thinking in Science” (8-12 November 2022). Title of the talk: “Design of photoswitchable ligands to allow the optical control of biological activity”.
• Dr. Castagna presented a poster the international conference “2nd  Drug Discovery Conference” organized by the Latvian Institute of Organic Synthesis (Riga, Latvia) 22-24 September 2022. Poster title: “A donor-acceptor Stenhouse adduct active in neuronal GABAARs and photoswitchable in water”.

International collaborations

• In the framework of the international collaboration with Prof. Elena Ishow form Nantes University (Nantes, France), which focuses on the development of innovative solution for the removal of bacteria from water, a joint grant application has been submitted for the International Emerging Actions IEA-2022 call (The proposal was submitted on 15th September 2022).
• Dr. Castagna was involved, as an associated partner, in the international grant proposal for the HORIZON-MSCA-DN-2022 call. The proposal, coordinated by Tampere University (Tampere, Finland), was submitted on 15th November 2022.

Outreach activity

Dr. Castagna actively participated in the “Researcher Night” event that was held at the LIOS on September 30th 2022. More than 1000 people attended this event, in which demonstration ranging from chemistry experiments to 3D molecular visualization was carried out by LIOS researchers.

Publication date 30.11.2022.

A first secondment visit at the Aix-Marseille University in the group of Prof. Frederic Andrè has been performed at the beginning of December 2022. During this stay, the small library of photoswitchable compounds developed by Dr. Castagna at the LIOS were tested in cell-cell adhesion assays, showing promising results. Based on the results on these functional assays, Dr. Castagna’s scientific activity at the LIOS has continued with the complete purification of the best performing compounds, as well as with the synthesis of new compounds. In parallel, a full photochemical characterization of all compounds is ongoing. A second visit to Aix-Marseille University is envisioned within the next 3 months to perform further functional cell-cell assays.

Training activities

• Dr. Castagna attended the online course “The development of a medical device” held by the Institute of Bioengineering of Catalonia on 21st December 2022.
• Dr. Castagna attended the online seminar “Strategies in Antimalarial Drug Discovery” organized by the EUopenscreen on 31.01.2023.
• Dr. Castagna attended the two days training course on kinetics measurements with CREOPTIX Wave rapid instrument organized at LIOS on 9-10th February 2023. The training included theoretical lessons and practical hands-on sessions.
• Dr. Castagna attended the 1-week course on “Cryo-Electron Microscopy” organized by LIOS and held (online) from Cambridge University on 20-24th February 2023. The workshop combined online lectures and practical sessions in a remote environment.

Grant awarded

Dr. Castagna has been awarded a bilateral Latvian-French Hubert Curien partnership grant (OSMOSE 2022) for the period 2023-2024. Title of the project: “Multimodal electrospun nanofibers for minute-trapping and removal of bacteria in water” (FIBOMAG). France partner: Prof. Eléna Ishow (Nantes University).

Publication date 28.02.2023.

During this period, the scientific activity proceeded with the synthesis and purification of new analogues of the compounds tested in Marseille during the secondment visit in December 2022. Functional and spectroscopic properties of these compounds are still under investigation. In the framework of this project, Dr. Castagna is currently supervising 2 students: one master student from the University of Pavia (Italy) and one trainee.

Sustainability and disseminating actions

• Dr. Castagna submitted a project application on the 7th March 2023: for the call Horizon Europe Pathfinder Open. Call: HORIZON-EIC-2023-
  PATHFINDEROPEN-01. LIOS Role: Partner unit, leader Dr. Castagna;
• Dr. Castagna submitted a project application on the 12th May 2023: for the M-ERA.NET 2023 call. LIOS Role: Partner unit, leader Dr. Castagna;
• Dr. Castagna submitted a grant application on the 15th May 2023 for the FLPP Fundamental and Applied Research Projects by the Latvian Research
  Council;
• Dr. Castagna participated in the “Biotechnology Breakfast” event organized by the Biocatalysis Foundation in cooperation with the Investment and
  Development Agency of Latvia (LIAA) in the framework of the DEEP TECH
  Atelier, which was held in Riga on 21/04/2023.

Training activities

• Dr. Castagna gave a training seminar to the whole group on
  “Photopharmacology: a palette of opportunities for photoswitchable molecules” on 28/04/2023 at the LIOS.

Appointments

• Dr. Castagna has been appointed Member of the COST Action CA21159 PhoBioS “Understanding interaction light-biological surfaces: possibility for new electronic materials and devices”.

Publication date 31.05.2023.

During this period, the scientific activity proceeded with the characterization and
functional assays of the compounds. The project partner, Prof. F. Andrè (University
of Marseille, France), has tested the compounds using cellular adhesion assays.
Also, the patentability of the compounds synthetized during the project is currently
being assessed. Meanwhile, Dr. Castagna is currently carrying out the complete
photochemical characterization of the compounds at the LIOS.
The trainee who has been incorporated into the project has concluded her training
programme. Dr. Castagna is continuing the supervision of one master student from
the University of Pavia (Italy).

Communication and dissemination actions

• Dr. Castagna is part of the organizing committee of the conference “Recent
  Advances in structural biology and drug discovery” that will be held in Riga on 18-
  19 th September 2023.

Awards

• Dr. Castagna has been shortlisted in the top 10 for the 2023 USERN Prize for
  young scientists in the section Biological Science. The selection of finalists and
  winner is currently on going (read more).
  
  

Publication date 31.08.2023.

During this period, the scientific activity proceeded with the characterization and functional assays of the compounds. The project partner, Prof. Frederic Andrè (University of Aix-Marseille, France), has tested the compounds using cellular adhesion assays.
The master student who has been incorporated into the project has concluded her training programme and submitted her thesis on “Towards the development of cell-cell adhesion inhibitors” to be discussed on December 2023 at the University of Pavia (Italy).

Communication and dissemination actions

• A patent covering the structure and activity of the compound developed during this project was submitted on 30.11.2023 (Patent number LVP2023000129).
• Castagna delivered an invited presentation at the USERN 2023 Conference held in Yerevan, Armenia (8-10 November 2023). The title of the presentation was “Designing Ligands for Photopharmacology: a palette of Opportunities for Photoswitchable Molecules”.

  On this occasion, she has been awarded the USERN 2023 Medal as a top 5 researcher in the field of  “Biological Science” for 2023.

  During the conference, she was elected USERN Joung Ambassador for Latvia to promote the activity of the network in Latvia.

• Castagna was part of the organizing committee of the conference “Recent Advances in Structural Biology and Drug Discovery” that was held in Riga on 18-19 September 2023.

Publications

• Hajar Estiri, Shapla Bhattacharya, Jhon Alexander Rodriguez Buitrago, Rossella Castagna, Linda Legzdiņa, Giorgia Casucci, Andrea Ricci, Emilio Parisini & Alfonso Gautieri. “Tailoring FPOX enzymes for enhanced stability and expanded substrate recognition” Scientific Reports 2023, 13, 18610. https://doi.org/10.1038/s41598-023-45428-1

Publication date 30.11.2023.