Partnership

Aalto-Helsinki x Team TU Dresden

Combining Q Block and WunderBand

On 13th June, the TU Dresden team contacted us to inquire about working together on our chronic wound projects, as we both have the same goal of accelerating their healing. Dresden's approach is a bit different, using phage display (instead of our ribosome display) to first remove the bacterial infection in the wounds, before applying growth factors to target tissue rebuilding. These would be applied via hydrogel.

We saw this as a great opportunity for a deep partnership, because our DARPin-based solution would act as a precursor to Dresden's project. This is how we envisioned our projects combining to form an effective treatment sequence, therefore fulfilling the Gold partnership criteria of reciprocity:

1. In the early stages of wound chronification, our DARPin would be applied to the wound via Dresden's hydrogel to slow down or completely prevent the formation of a biofilm layer, by blocking the AIP signalling molecules released by any early colonising Staphylococcus epidermidis. This would make debriding of any existing biofilm easier, or an avoidable step altogether.
2. Next, Dresden's phages would be applied to the wound via hydrogel to kill any infectious bacteria that did manage to settle at the wound site. This again makes the debriding process easier for clinical staff, and the wound site is left clean for the following phase of healing.
3. Dresden's growth factors would finally be applied to the wound via hydrogel to stimulate angiogenesis and tissue reconstruction, speeding up actual closure of the wound.

Partnership in Dry Lab and Wet Lab

To reciprocally inform and develop each other's projects in unison, we have partnered on the following steps:

• DRY LAB
  Help from Dresden on computation modelling the passage of the DARPin through the biofilm matrix, adding an extra proof-of-concept to our own modelling of protein-peptide docking. For Dresden, this has served as a valuable test that their modelling methods are applicable to new molecules beyond the phages and growth factors they were initially testing them on.
  More details regarding the computational modelling can be found on the Model page.
• WET LAB
  Worked together on a suitable biomaterial for applying both our DARPins and Dresden's molecules to the wound site - this is continuing with Dresden's hydrogel idea but expanding it to usage with DARPins. For this, we sent our GFP DARPin, which was freeze-dried, via post directly to Dresden for them to use in their lab. This area of partnership is, again, reciprocally useful for both of our teams and projects. First, it develops for us a medium through which to apply the DARPin to the wound site and to understand the diffusion constant through the material, informing how much DARPin is required to be concentrated in the hydrogel to inhibit a sufficient concentration of AIPs; it also informs us about the stability of DARPins and how they move through a hydrogel medium, e.g. whether they aggregate or are too slow in passing through it. For Dresden, this information provides additional proof of concept about the utility and versatility of their designed hydrogel. Importantly, knowledge about the diffusion rate of the DARPins can be helpfully compared to that of phages and growth factors, allowing Dresden to better estimate how different molecular weight proteins pass through the hydrogel and which combination may be ideal for maximum wound healing. Finally, these tests are a key element of eventually commercialising a hydrogel and scaling its use in a clinical setting, as it is crucial to prove that it remains a stable material in the presence of different types of therapeutic molecule as well as capable of releasing these at a favourable rate.

History of Meetings

We first met the Dresden team via Zoom on 20th June and presented our projects to each other, particularly our current state of progress, what we hope to achieve in the next few months. We were then better able to draw parallels between our solutions and brainstorm our points of partnership. We then met the Dresden team face-to-face at the European meet-up in Hamburg, Germany, 1st-3rd July. We also had the chance to meet them at the Junior Jam in Münster, Germany, 26-28th August.