WEBVTT NOTE This file was generated by Descript 00:00:04.056 --> 00:00:07.455 Our immune system guards the body by recognizing and defending 00:00:07.455 --> 00:00:10.856 against bacteria, viruses, and other harmful invaders. 00:00:11.176 --> 00:00:14.456 But the immune system can overreact or start attacking the body's 00:00:14.515 --> 00:00:16.705 own tissues, leading to diseases. 00:00:17.056 --> 00:00:20.886 For the past 10 years, Professor Feng Shao's team has been focusing 00:00:20.895 --> 00:00:24.096 on unraveling the molecular mechanisms underlying host 00:00:24.105 --> 00:00:25.945 cell inflammatory responses. 00:00:26.186 --> 00:00:32.625 I was studying how does a particular bacteria cause disease or infect 00:00:32.766 --> 00:00:37.686 our body or our cell, and we know that different bacterial pathogens, 00:00:37.726 --> 00:00:39.355 they have different mechanisms. 00:00:39.775 --> 00:00:44.916 So what we learn from there cannot be generalized to the broader level. 00:00:45.686 --> 00:00:49.056 As a scientist, we always want to look for something new and do 00:00:49.056 --> 00:00:52.496 something that we have never done that will get you more excited. 00:00:53.006 --> 00:00:56.815 So that's the reason I decided to shift to the innate immune research. 00:00:57.185 --> 00:01:02.135 This system works broadly to detect all kind of bacteria infection and 00:01:02.135 --> 00:01:06.095 even other microbial infections, so the results could have a bigger impact. 00:01:06.646 --> 00:01:13.696 So LPS, which we call lipopolysaccharide, is a large molecule, is the most abundant 00:01:13.875 --> 00:01:20.730 structural component of the cell wall of Gram-negative bacteria In our field 00:01:20.760 --> 00:01:26.610 LPS is considered the most important molecule for bacteria to survive as 00:01:26.620 --> 00:01:31.770 well as a major molecule detected by the immune system because as the immune 00:01:31.770 --> 00:01:35.930 system, we need to detect the infection, and the way to detect the infection 00:01:35.939 --> 00:01:38.799 is to recognize something abundantly. 00:01:38.799 --> 00:01:43.110 How LPS is recognized in host cells was not clear, and the responsible pattern 00:01:43.110 --> 00:01:44.940 recognition receptor was unknown. 00:01:45.340 --> 00:01:49.009 Shao found that inflammatory caspases, a family of proteolytic 00:01:49.010 --> 00:01:53.079 enzymes that can induce cell death and inflammation, caspase-4 and -5, 00:01:53.079 --> 00:01:55.670 are intracellular receptors for LPS. 00:01:55.900 --> 00:01:59.140 They can directly recognize LPS and become activated, then 00:01:59.150 --> 00:02:01.010 triggering host immune reactions. 00:02:01.320 --> 00:02:04.980 He also discovered that gasdermin D is the downstream death effector 00:02:04.980 --> 00:02:06.660 of the inflammatory caspases. 00:02:06.770 --> 00:02:12.280 There is a family or a group of proteins that all share the pore-forming 00:02:12.300 --> 00:02:14.510 activity we call a g- gasdermin family. 00:02:14.620 --> 00:02:18.990 When they are activated, and they will also do the same thing to make pores and 00:02:18.990 --> 00:02:24.370 to kill cells by pyroptosis, which is the pro-inflammatory form of cell death. 00:02:24.420 --> 00:02:28.409 Conceptually, the finding actually is paradigm shifting because 00:02:28.540 --> 00:02:33.000 previously on studies on cell death are focused on the caspase. 00:02:33.080 --> 00:02:38.720 So the discovery of gasdermin D means that there are molecules downstream of caspase. 00:02:39.019 --> 00:02:43.950 Those molecules are executor proteins in the cell death pathway. 00:02:43.950 --> 00:02:48.929 So that changes our mindset about understanding the execution of cell death. 00:02:49.129 --> 00:02:53.810 By manipulating gasdermin proteins, it is possible to control inflammatory responses 00:02:53.810 --> 00:02:58.070 of the body, paving the way for developing potential drugs for serious inflammatory 00:02:58.070 --> 00:02:59.840 diseases and possibly cancers. 00:02:59.990 --> 00:03:04.000 The discovery of gasdermin essentially provides a novel drug 00:03:04.050 --> 00:03:06.829 target to manipulate inflammation. 00:03:07.350 --> 00:03:12.250 So if we block gasdermin activation, that might help provide some 00:03:12.250 --> 00:03:15.910 clinical benefits in treating inflammatory disease like sepsis. 00:03:16.360 --> 00:03:19.260 Shao tends to question the conventional beliefs in biology. 00:03:19.469 --> 00:03:23.130 This mantra helps him find the necessary breakthroughs in identifying 00:03:23.150 --> 00:03:25.180 caspases as the LPS receptor. 00:03:25.620 --> 00:03:29.360 With a team that has diverse backgrounds, Shao's team is unafraid to try new 00:03:29.360 --> 00:03:31.090 experimental methods and tools. 00:03:31.360 --> 00:03:35.049 For instance, the discovery of gasdermin protein involved the use of 00:03:35.049 --> 00:03:39.600 CRISPR-Cas9 genome editing technology, which was quite new when first applied. 00:03:40.040 --> 00:03:42.170 So I came from a chemistry background. 00:03:42.170 --> 00:03:46.210 I gradually moved to biochemistry, biology, and now 00:03:46.240 --> 00:03:48.200 immunology and medical science. 00:03:48.550 --> 00:03:52.420 The direction of my career pursuit has always been to do something 00:03:52.459 --> 00:03:56.840 useful in clinics to help us to understand disease and treat disease. 00:03:56.950 --> 00:04:01.309 The 2019 Future Science Prize in Life Science was awarded to Feng 00:04:01.309 --> 00:04:04.870 Shao for his seminal discoveries of cytosolic LPS receptors and 00:04:04.870 --> 00:04:09.060 downstream effectors in inflammatory responses to pathogenic bacteria.