Notebook

Weekly Progress

Click on each week for more details.

Before Lab work (Dec 23-July 24)
    Recruitment (December-January)
  • Applications to join the team were due by 1st December
  • Interviews with members of the CU Synthetic Biology Society committee were carried out during December
  • The team was finalised in mid-January

  • Brainstorming and training (January-March)
  • Weekly brainstorming sessions to discuss and develop project ideas
  • Information sessions on synthetic biology, iGEM, human practices, etc.,
  • Meetings with academics and industry experts for advice on idea feasibility

  • Detailed project design (Early July)
  • Literature review on previous methods in magnetogenetics and possible pathways that could be manipulated e.g. EGFR, EPG, Hog1, HSF1, MscS, Piezo, Ste2, TcI, TlpA, Wsc1
  • Literature review on magnetic nanoparticles and their purchase and synthesis
  • Meetings with academics for advice on project feasibility and suggestions

  • Getting ready for lab work
  • Risk assessment for iGEM and the Department of Engineering lab space
  • Created template for wet lab notebook
  • Discussed logistics of ordering reagents and plasticware with advisors
  • Parts mining for plasmid design through iGEM registry and scientific papers
  • Workshop on primer design
  • Induction and training in lab
  • Researching and compiling protocols
  • Inventory of items left by previous iGEM teams
  • Design and ordering of primers and gene fragments for the construction of plasmids needed to test EPG, TlpA, and TcI
  • Design of AFM circuit and fluorometer

  • Outreach
  • Designing materials for Smallpeice outreach event

Week 1 (15/07-21/07)
    Wet lab
  • Receiving, suspension, and storage of primers
  • Receiving and preservation of required E. coli and S. cerevisiae strains for TlpA/TcI, Wsc1, HSF, and EPG pathways
  • Test of antibiotics that are required for transformation
  • Preparation of competent cells for Golden gate
  • PCR of parts required for Golden gate

  • Hardware
  • Box no.1, for imaging plates on the large electromagnet, constructed
  • Raspberry Pi 3 obtained

  • Modelling
  • Modelling workshop with instructor
  • Construction of ODE model for TlpA, TcI, and Wsc1 started
  • Literature review on model parameters

  • Human Practices
  • Start reading on neuroscience, organoid, and policies
  • Start communication with academics

Week 2 (22/07-28/07)
    Wet lab
  • Antibiotics testing
  • Test transformation of pUC19 and luciferase from the kit to test the competency of competent cells and efficiency of chemical transformation protocol
  • Start transformation of kit parts required for all pathways and get ready for the golden gate
  • Yeast HSF pathway construction starts
  • 250 nm magnetic nanoparticles visualisation with a light microscope

  • Hardware
  • ZVS heating of ferrofluids obtained from Cavendish lab
  • ZFS coil parameter analysis
  • Design of box with moving magnets and imaging system

  • Modelling
  • Construction of model calculating forces generated by 250 nm magnetic nanoparticles started

  • Human Practices
  • Detailed feedback from researchers in organoid development and neuroscience
  • Plan for structures of human practices deliverable

Week 3 (29/07-04/08)
    Wetlab
  • Attempting minipreps on previously transformed cells
  • Validation of miniprep parts on gel
  • Troubleshooting chemical transformation
  • Testing and trials of electroporation
  • Continuous working on TlpA/TcI pathway construction
  • More MNP observation under light microscope, observing random movement change to biassed movement upon application of a magnetic field

  • Hardware
  • Coil design iterations

  • Modelling
  • Modelling of magnetic field shape and strength, used to inform coil design iterations
  • Modelling of nanoparticle heating and dissipation of heat across plate
  • Modelling of the HSF and Wsc1 pathways

  • Human Practices/Outreach
  • Making the table of stakeholder areas and people we have communicated with
  • Making a comparison table of sonogenetics, optogenetics, magnetogenetics, and chemical methods
  • Contacting more stakeholders in a more diverse range
  • Biomedical engineering summer course outreach event

Week 4 (05/08-11/08)

    Wet lab
  • Chemical transformation has relatively low efficiency. Electroporation works better. We’re switching the transformation method to electroporation
  • Previous miniprep is not working and we need to re-transform all parts required.
  • Construction of EPG pathway starts
  • First attempt at golden gate assembly parts available for TlpA/TcI

  • Hardware
  • Testing of relays, servo, camera, thermal camera, motors, and display
  • Initial development of GUI for control and measurement of magnet

  • Modelling
  • Further iterations on modelling of TlpA/TcI, HSF, and Wsc1 pathways
  • Calculation of magnetic field gradient
  • Calculation of force acting on magnetic nanoparticles in water
  • Modelling of further EPG constructs, with LacI and TEV

  • Human Practices
  • Meeting with Stuart Ibsen about sonogenetics - costs of technology, how the technology works, use cases.
  • Meeting with Mightex about optogenetics - found out rough costs of equipment and cost ranges. Found out more about who is using optogenetics (mostly universities).

Week 5 (12/08-18/08)

    Wet lab
  • Golden gate of EPG started
  • MNPs attachment test to see if MNPs bind to his-tagged Wsc1
  • Preparation and testing for yeast Leu- Ura- His- selection plate
  • Transformation of Y1 for Wsc1 pathway
  • Miniprep is not working, figuring out what's the problem and changing the kit for miniprep
  • Troubleshooting of previous TlpA / TcI golden gate by gel and digest validation

  • Hardware
  • Development of imaging system
  • Further design of the “magenta” box with the moving magnet

  • Modelling
  • Further modelling on HSF and discussion with the instructor about the temperature function
  • EPG-TEV model constructed

  • Human Practices
  • Meeting set up with neuro-oncologist at Addenbrooke’s next Tuesday 10am
  • Responses from CAR-T cells researcher
  • Girls in Math educational event at St Johns’ college Cambridge

Week 6 (19/08-25/08)
    Wet lab
  • Transformation of Y1 with pHPS100H for wsc1 construct
  • Testing of X-gal and sorbitol on HAS100L
  • Golden gated plasmids are not working. We need to check from the parts, miniprep, transformation, golden gate with gel validation to see what went wrong

  • Hardware
  • Construction of the “magenta” box with the moving magnet and imaging system

  • Modelling
  • Initial model of HSF finished and had a discussion with the instructor
  • Integrating HSF model with thermal magnetic modelling

  • Human Practices
  • Meeting with Dr Rajesh Jena (neuro-oncologist) who had a lot of interesting thoughts about glioblastoma recurrence prevention and CAR T-cell therapy application ideas
  • Draft of Education page

Week 7 (26/08-01/09)
    Wet lab
  • Successful transformation of Y1 with pHPS100H. Conducting sorbitol and X-gal test on Y100H to validate the construct is working
  • MNPs binding test to Wsc1
  • Golden gate troubleshooting
  • Toxicity test of 20 nm MNPs on E. coli DH5alpha and BL21
  • Re-transforming, miniprep, digest, and golden gate the parts

  • Hardware
  • Testing on a large coil to validate if a magnetic field with a low frequency, high field strength could be produced
  • 20 nm MNPs heated up when a magnetic field with high frequency and high field strength was applied

  • Modelling
  • Improvement of TcI and Wsc1 modelling

  • Human Practices
  • Preparation of posters and slides that will be used for UK 2024 iGEM meetup at Sheffield

Week 8 (02/09-08/09)
    Wet lab
  • The transformation and direct miniprep did not work well, and we decided to colony PCR the parts we need and validate it
  • Figuring out a working protocol to conduct X-gal testing on yeast
  • Testing of sonicator on liquid X-gal testing with yeast
  • Wsc1 MNPs testing with magnetic field in a liquid based culture
  • Toxicity testing of yeast with 250 nm MNPs
  • Continuous attempts of golden gate of EPG parts

  • Hardware
  • Set up the algorithm for the camera fluorescence measuring
  • Movement of magnets, and calibration with limit switches
  • Testing on the motor.

  • Modelling
  • Further improvement of modelling of TlpA/TcI and EPG

  • Human Practices
  • Writeup in progress
  • UK iGEM Meetup 2024 this weekend

Week 9 (09/09-15/09)
    Wet lab
  • Colony PCR of EPG, validation with gel, transformation with BL21 and test with nanoluc
  • MNPs-resuspended in LB agar and testing the bacterial growth and heating of the plate
  • Arrival of synthesised TlpA and TcI constructs
  • Miniprep of TlpA and TcI constructs from Dh5alpha
  • Wsc1 MNPs testing with magnetic field in both solid and liquid method

  • Hardware
  • Software set-up and testing interactions of the “magenta” box
  • Camera test and calibration

  • Modelling
  • Summarising TlpA and TcI modelling

  • Human Practices
  • Writeup approaching the end

Week 10 (16/09-22/09)
    Wet lab
  • Colony PCR, miniprep, and gel validation of EPG and TcI construct
  • Troubleshooting of the TcI construct
  • Heat-testing of TcI and testing of EPG luminescence with magnet

  • Hardware
  • New coil design and ferrofluid heating test
  • Testing of three constructed boxes with instructors and getting user’s feedback

  • Modelling
  • Summary of all models (TlpA/TcI, wsc1, HSF, magnetic force, magnetic heating) and final writeup planned

  • Human Practices
  • Write-Up content done. Planning the final format to be displayed on wiki

Week 11 (23/09-29/09)
    Wet lab
  • Colony PCR, miniprep, and gel validation of TcI construct
  • Repeats of TcI heat-activation to test new golden gate 1pV3
  • Miniprep of some constructs for sequencing
  • Summarising all testing results and uploading new basic parts/constructs to iGEM registry

  • Hardware
  • Construction of the final box finished
  • Hardware writeup in progress

  • Modelling
  • Summarising all models. The final write up is uploaded to wiki

  • Human Practices
  • Write-Up content uploaded to wiki

Detailed wet lab notebook

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