Alireza Hekmati — HTGAA 2025

My Name in ZOOM: Alireza Hekmati, Bujnord, Iran.
My Name in Slack: Alireza Hekmati (Committed listener)
Assignments
- Week 1: Principles and Practices
- Week 2: DNA Read, Write, and Edit
- Week 3: Lab Automation
- Week 4: Protein Design Part I
- Week 5: Protein Design Part II
- Week 6: Genetic Circuits Part I
- Week 7: Genetic Circuits Part II
- Week 9: Cell Free Systems
- Week 10: Bio Production
- Week 11: Building Genomes
- Week 12: Imaging and Measurement
- Week 13: Bio Design, Living Materials
- Week 14: Frugal Science, Microbiome
Projects
Mindmap
mindmap
root((HTGAA 2025))
AI + Computational Bio
Multi-omics → LLM orchestration
Genomics / Transcriptomics / Proteomics / Metabolomics
Indirect pulls from DBs; NCBI, UniProt, KEGG, Reactome
AI protein/peptide design
PepMLM from HuggingFace for peptide generation
Structure prediction + docking/MD
Binder design: AfDesign / RFdiffusion / EvoBind / BindCraft
Automation & coding
Google Colab protocols → Opentrons robots
Scale experiments, iterate fast
Protein Science & Design
Amino acids & stereochemistry
L vs D amino acids, helix handedness
Secondary structure
α-helices & variants, β-sheets → aggregation
Amyloids as stable materials
Model protein
eGFP: primary→tertiary structure characterization
Genetic Engineering Methods
DNA read/write/edit basics
Gel electrophoresis, Benchling workflows
PCR chemistry
Phusion HF Master Mix components/purpose
Assembly
Gibson Assembly
Cloning & expression
Vector design → E. coli expression
Regulatory Logic & Circuits
Post-transcriptional vs post-translational control
Endoribonucleases for RNA cleavage vs proteases for protein degradation
Cell-Free Systems
Why cell-free?
Speed - no culturing!
Open control of DNA, amino acids, energy, enzymes
Toxic proteins OK; supports UAAs
Bioproduction & Pathways
Carotenoids in E. coli
crtE + crtI + crtB → lycopene
+ crtY → β-carotene
Automation mindset
What new questions when everything is automated?
Phage Engineering: MS2
Lysis protein L
N- vs C-terminal roles; C-term TM drives lysis
33-nt non-overlapping window
Introduce stop codon to split N from C → DnaJ-independent lysis
Preserve overlaps with cp/rep genes
Mitochondrial Therapeutics
Target: Cyclophilin D "CypD"
Block mPTP opening in I/R injury
Design peptide inhibitor; plan in vitro/in vivo validation
Knowledge Sources
NCBI GenBank • UniProt • KEGG • Reactome