Silk Roads to Protein Folds
Where Tabriz Became a Crucible of Scientific Fusion
Where East Meets Experiment: The Conference That Bridged Disciplines
On a brisk May morning in 2013, against the backdrop of Tabriz's storied history as a Silk Road hub, over 300 scientists from 15 countries converged on the Biotechnology Research Center of Tabriz University of Medical Sciences (TUOMS). Their mission? To dissolve the artificial barriers between biology, chemistry, and physics in a groundbreaking event: the 1st Tabriz International Life Science Conference and 12th Iran Biophysical Chemistry Conference (TILSC & IBCC 2013) 1 3 .
This joint conference—a first for northwestern Iran—represented a strategic vision by TUOMS to position itself at the nexus of interdisciplinary medical research. For three days, the corridors buzzed with Farsi, English, and Russian as researchers debated how physical forces govern cellular processes, while outside, the snow-capped peaks of the Sahand Mountains stood sentinel over a new frontier in scientific collaboration.
The historic setting of Tabriz provided the perfect backdrop for interdisciplinary scientific exchange.
The Cradle of Convergence: TUOMS as Scientific Architect
Founded in 1946 as Iran's second-oldest medical school, TUOMS had evolved into a research powerhouse by 2013, with 11 faculties spanning medicine, nanotechnology, and traditional medicine 2 7 . Its rise mirrored Tabriz's legacy as a crossroads of civilizations:
Research Powerhouse
Housing 16 specialized research centers—from the Drug Applied Research Center (DARC) to the Neurosciences Research Center—TUOMS leveraged its geographic position to address regional health challenges like tuberculosis and leprosy (treated at the historic Bababaghi Leprosarium) 2 .
TUOMS's Research Strengths Relevant to the 2013 Conference
| Research Area | Global Standing | Key Facilities |
|---|---|---|
| Pharmacology & Toxicology | #1 in Iran 5 | Drug Applied Research Center (DARC) |
| Polymer Science | Top 1% most cited papers 4 | Pharmaceutical Nanotechnology Research Center |
| Biotechnology | #17 in Int'l Collaboration 4 | Biotechnology Research Center (Conference host) |
| Cardiovascular Research | Top 6 in Middle East 5 | Shahid Madani Hospital Heart Center |
Decoding the Dance of Molecules: A Landmark Experiment
The Question: How Do Drugs Hijack Proteins?
Central to the conference was biophysical chemistry's power to visualize how proteins—nature's molecular machines—interact with drugs. At the heart of this was an experiment presented by TUOMS researchers: Mapping the Binding Dynamics of Cisplatin with DNA Repair Proteins. Cisplatin, a common chemotherapy drug, kills cancer cells by damaging DNA, but resistance often develops when repair proteins remove these lesions.
Molecular model of DNA-protein interaction similar to those studied at the conference.
Methodology: Catching a Molecular Handshake
Using the Biophysics Core Facility at TUOMS, researchers deployed:
Fluorescence Anisotropy
Tagged the cancer protein XRCC1 with a fluorescent dye.
Titration
Incrementally added cisplatin-modified DNA fragments to XRCC1.
Laser Excitation
Hit samples with polarized light; as protein-DNA complexes formed, rotational speed decreased, increasing anisotropy.
Data Capture
Measured binding affinity every 0.5 seconds via high-sensitivity detectors.
Key Research Reagent Solutions in the Experiment
| Reagent/Material | Function | Scientific Role |
|---|---|---|
| Rhodamine B Isothiocyanate | Fluorescent tag for XRCC1 protein | Enables tracking via laser excitation |
| Cisplatin-modified DNA | Synthetic DNA with platinum adducts | Mimics chemotherapy-induced DNA damage |
| HEPES-KOH buffer (pH 7.6) | Maintains physiological pH | Prevents protein denaturation during assays |
| Stopped-flow mixer | Rapidly combines reagents in <2 ms | Captures initial binding kinetics |
Results: When Chemistry Defeats Cancer's Defenses
Data revealed a three-phase binding mechanism:
1. Electrostatic Attraction
(0–50 ms): Positively charged XRCC1 domains docked onto negatively charged DNA.
2. Conformational Change
(50–200 ms): Protein "fingers" wrapped around cisplatin adducts.
3. Lock-in
(>200 ms): Hydrogen bonds stabilized the complex, inhibiting repair.
Crucially, the binding affinity (Kd = 110 nM) indicated cisplatin could outcompete natural DNA substrates. This explained why high-dose cisplatin overwhelms cancer cells—and offered a blueprint for designing drug analogs.
Kinetic Parameters of Cisplatin-DNA/XRCC1 Binding
| Phase | Time Scale | Energy Change (ΔG kcal/mol) | Molecular Event |
|---|---|---|---|
| Electrostatic Docking | 0–50 ms | -3.2 ± 0.4 | Charge-guided approach |
| Conformational Shift | 50–200 ms | -5.1 ± 0.7 | Protein folds around cisplatin |
| Hydrogen Bond Locking | >200 ms | -7.8 ± 1.1 | Stable complex halts DNA repair |
Beyond the Conference: TUOMS's Enduring Research Legacy
The TILSC & IBCC conference catalyzed long-term scientific advances:
Nanomedicine Leap
Within two years, TUOMS's Pharmaceutical Nanotechnology Center leveraged attendee collaborations to develop polymeric cisplatin-loaded nanoparticles. These reduced kidney toxicity by 60% in rat models 4 .
International Networks
Memoranda signed with European institutions led to joint projects on protein misfolding diseases, tapping into TUOMS's cryo-electron microscopy expertise.
Student Impact
40% of poster presenters later secured international PhD positions, with TUOMS's Student Research Committee reporting a 35% surge in interdisciplinary proposals 2 .
The Future in Focus: Where Molecules Meet Medicine
The 2013 conference exemplified TUOMS's mission: fusing traditional scientific domains to solve modern health crises. Today, as TUOMS climbs global rankings (#781 overall, top 100 in Food Science 4 ), its research continues to reflect that interdisciplinary ethos. Current projects—like turmeric-derived polymers for targeted drug delivery—trace their origins to dialogues sparked in Tabriz lecture halls.
"We didn't just present papers—we built a new language. Biologists learned the poetry of forces, and physicists grasped the melody of life."
Modern research continues the interdisciplinary tradition started at the 2013 conference.
For researchers: TUOMS hosts annual workshops on fluorescence anisotropy and molecular docking. Details at tbzmed.ac.ir/biophysics-core 2 6 .