From Protein Toxins to Applied Toxicological Testing

Topics for Discussion (~ 40 min. per topic) 1. Is a harmonized toxin database needed? (i.e, a single DB) a) Toxins vs. allergens; DB usefulness vs. toxicity information b) Toxicity is defined by protein function; allergenicity is defined by IgE binding (not depending on protein function) c) Input from Toxin biologists d) Do we need an additional database or Do we need a Tool to navigate across all databases already available? 2. Toxin Definition a) How to decide what goes into a DB (criteria)? (e.g., nature – mammalian toxins?) b) Toxin/anti-toxin (how does anti-toxins fit the definition? Why would they be in a DB?) c) Sorting of toxins (level of toxicity) - target organism would impact sorting; impact of “effectors”. 3. Toxin Sequence List/Database a) Continuation of Day-2 discussion / Comparison with Industry DBs 4. Tools for assessing toxins a) Sequence similarities b) Thresholds i. Does this apply to engineered proteins? What if 3 aa changes? c) Tools (single or series of tools) d) Best ways to use primary sequence & structural data to predict toxins? (e.g., Pfam) e) Where bioinformatics could take us? (could inform functionality; could also inform about alignments). Understanding limitations of tools 5. Back to first question: Is a harmonized toxin database needed? 6. Future steps - where do we go from here? a) 3Rs? (Refine, Replace, Reduce) b) Tier-1 (ID hazard) & Tier-2 (characterize hazard; tox studies) - (Delaney paper) i. Is tier-2 always needed? What factors prompt a “go/no go decision” for tier-2? (future steps)?