Department of Molecular Probes and Prodrugs


 

Head:

Jacek Ł.Kolanowski,PhD

 


 

Staff:

Michał Gładysz, PhD

Bartosz Marciniak, PhD

 

 


 

PhD Students:

Francesca Canyelles I Font

Reza Pashaei

 


 
 

 

Rys.1

 

 

Rys.2

 

 

Rys.3

 

 

Rys.4

Keywords:

Molecular probes, fluorescence, bioluminescence, microscopy, chemical biology, biological chemistry, live-cell imaging, cell lines, assays, HTS, high throughput screening, free radicals, metal ions, proteins/enzymes, biomarkers, prodrugs.

 

Research area:

 

Chemical tools for (a) detection and (b) modification of interactions in live cells

 

The main aim is to develop low-molecular weight chemical tools to image, study and control biological systems through mapping and subsequently modifying interactions between biochemical targets in live cells (figure). In particular:

- Fluorescent and bioluminescent molecular probes for sensing pairs of analytes to associate biochemical changes inside cells with the development of disease (e.g. lung and prostate cancer).

- Non-genetic methods for in situ tagging of endogenous proteins to visualise endogenous proteins and study their interactions in live cells.

- Multiplexing assays (based on small molecules) for high-throughput screening to improve the identification of most promising small molecule drug candidates and deciphering their mechanism of action (also within the ERIC EU-Openscreen  consortium and POL-Openscreen initiative)

These tasks encompass, among others:

- Organic synthesis of probes (low molecular weight fluorophores and bioluminophores)

- Comprehensive spectroscopic analysis (in cuvettes and on microplates)

- Assay development and microscopic imaging of live cells through confocal microscopy (including e.g. FRET and FLIM)

In collaboration:

- Flavin-based fluorescent probes and singlet-oxygen generators (prof. Marek Sikorski at the Faculty of Chemistry, Adam Mickiewicz University in Poznan)

 

Ongoing research projects:

1. Masked bioluminogenic substrates for a selective imaging of the biochemical parameters of cancer.

NCN – SONATA 13

2. MultiGATE: dual-analyte responsive fluorescent probes for a real-time multi-parametric sensing in cellular models.

FNP - HOMING 4

 

Selected publications from the last three years:

1. Z Lim, DG Smith, JL Kolanowski, RL Mattison, JC Knowles, S-Y Baek, W Chrzanowski, EJ New
A reversible fluorescent probe for monitoring Ag(I) ions.
Journal of the Royal Society Interface (2018),in press

2. KL Chong, BA Chalmers, JK Cullen, A Kaur, JL Kolanowski, BJ Morrow, K Fairfull-Smith, MJ Lavin, NL Barnett, EJ New, MP Murphy, SE Bottle*
Pro-fluorescent mitochondria-targeted real-time responsive redox probes synthesised from carboxy isoindoline nitroxides: Sensitive probes of mitochondrial redox status in cells.
Free Radical Biology & Medicine, in press

3. IJ Carney, JL Kolanowski, Z Lim, B Chekroun, TW Hambley, EJ New*
A ratiometric iron probe enables investigation of iron distribution within tumour spheroids.
Metallomics,10(4), 553-556 (2018)

4. JL Kolanowski+, F Liu+, EJ New*
Fluorescent probes for the simultaneous detection of multiple analytes in biology.
Chemical Society Reviews, 47, 195-208 (2018)

5. JL Kolanowski, LJ Dawson, L Mitchell, Z Lim, ME Graziotto, WK Filipek, TW Hambley, EJ New*,
A fluorescent probe for investigating metabolic stability of active transplatin analogues. Sensors and Actuators B: Chemical, 255 (3), 2721-2724 (2018)

6. PJ Wright, JL Kolanowski, WK Filipek, EG Moore, S Stagni*, EJ New*, M Massi* Versatility of terpyridine functionalised aryl tetrazoles: photophysical properties, ratiometric sensing of zinc cations and sensitisation of lanthanide luminescence.
European Journal of Inorganic Chemistry, 44, 2560-2570 (2017)

7. A Wu+, JL Kolanowski+, BB Boumelhem, R Lee, A Kaur, ST Fraser, EJ New*,
LM Rendina*
A New Carborane-Containing Fluorophore as a Stain of Cellular Lipid Droplets.
Chemistry – An Asian Journal, 12, 1704-1708 (2017)

8. ES O’Neill, JL Kolanowski, PD Bonnitcha, EJ New*
A cobalt(II) complex with unique paraSHIFT responses to anions.
Chemical Communications, 53, 3571-3574 (2017)

9. K Yang+, JL Kolanowski+, EJ New*
Mitochondrially targeted fluorescent redox sensors.
Interface Focus 7, 20160105 (2017)

10. JL Kolanowski, C Shen, EJ New*,
Fluorescent probes for the analysis of labile metals in brain cells.
Neuromethods, 124, Metals in the Brain pp 51-70 – invited book chapter. (2017)

11. C Shen, JL Kolanowski, CM-N Tran, A Kaur, MC Akerfeldt, MS Rahme, TW Hambley, EJ New*
A ratiometric fluorescent sensor for the mitochondrial copper pool.
Metallomics, 8, 915-919 - invited special issue. (2016)

12. ES O’Neill, JL Kolanowski, GH Yin, KM Broadhouse, SM Grieve, AK Renfrew, PD Bonnitcha, EJ New
Reversible Magnetogenic Cobalt Complexes.
RSC Advances, 6, 30021-30027 (2016)

13. JL Kolanowski, A Kaur, EJ New*,
Selective and reversible approaches towards imaging redox signaling using small molecule probes.
Antioxidants & Redox Signalling, April, 713-730 – invited (2016)

14. A Kaur, JL Kolanowski, EJ New*
Reversible fluorescent probes of biological redox state.
Angewandte Chemie International Edition in English, 55, 1602-1613 (2016)