My own story: How I got into this field

TPD, the short for “Targeted Protein Degradation”, is a popular term in recent biomedical cover stories. It denotes a series of biological and chemical approaches to trigger the degradation of certain target proteins by taking advantages of cellular protein degradation machineries. In other words, manipulating the cellular machineries to attack and degrade proteins of interest specifically. Sounds fantastic, right?

I’ve been fascinated by protein degradation techniques since my college, when I first learned the term “degron”. Degron is usually a short peptide sequence embedded in fast-turnover proteins such as cyclins in dividing cells. Those cyclins have short half-lives and degrade very fast. Scientists found out that their amino acid sequences have some special motifs that results in the fast turnover and fusions of these motifs to other proteins with longer half lives will get them degraded. Amazing!

Later when I joined Dr. Wu’s group in Tsinghua University, one of my senior colleagues tried to apply a tunable degradation domain (DD, by Promega) to her protein. The DD-fused proteins degraded fast but when you introduced a drug called Shield-1, they accumulated in the cells, thus allowing her to check the functional readout at a controllable manner.

When it came to my own PhD thesis, I chose a project on PROTAC.

To be continued. Please expect a series of update by the end of 2022.