TWiP 254: Our Hero Dickson - A Tribute and Deep Dive into Trypanosoma brucei Antigenic Diversity
0:00 Introduction and Tie: Hosts Daniel Griffin (wearing a Trichomonas vaginalis tie) and Christina Naula join Vincent Racaniello.
2:14 Tribute to Dickson Despommier: The episode begins with a tribute to the late Dickson Despommier, a long-time co-host of TWiP and a renowned parasitologist.
2:36 Christina's reflection: Dixon started the twip hero segments, and was much more than a parasitologist.
3:18 Dixon's early life: Born June 1940 in New Orleans, grew up in California, then moved to New York. He always spoke fondly of New Orleans.
3:50 Academic Career: He earned degrees in biology and parasitology, including a PhD from the University of Nottingham (1967) focusing on Trichinella spiralis.
4:38 Columbia University: He worked at Columbia for 28 years, researching Trichinella spiralis and the nurse cell, which is featured in the TWiP icon photo.
5:56 Teaching Career: Dixon taught parasitology to medical students at Columbia and was known for his engaging lectures.
6:28 Career Shift: After his lab closed in 1999, he developed a medical ecology course and became interested in vertical farming, inspired by Rene Dubos.
7:02 Vertical Farming Expertise: He authored books and taught classes on vertical farming and sustainable cities.
8:30 Published Author. Dixon wrote a book called People, Parasites, and Plowshares.
8:35 Photography: Dixon was a talented photographer, capturing images of nature, urban environments, and notably, salmon and trout flies.
10:23 Podcast History: Vincent recounts the history of TWiV (started in 2008) and TWiP (2009) with Dixon, as well as the short-lived Urban Agriculture podcast.
12:32 Parasitology Course: Dixon and Daniel taught a parasitology course, available on YouTube, which is highly recommended.
13:22 Fishing Both Vincent and Daniel share stories about fishing and Dixon.
16:07 Fond Remembrances: The hosts share memories of Dixon's personality, storytelling, and social nature.
19:59 Scientific Discussion - Trypanosoma brucei Paper: The hosts transition to discussing a research paper: "Tissue spaces are reservoirs of antigenic diversity for Trypanosoma brucei" (Nature, 2024).
21:36T. brucei Life Cycle Review: Daniel reviews the T. brucei life cycle, emphasizing the role of the tsetse fly and the parasite's stages in both the insect vector and mammalian host.
23:54 Winterbottom's Sign: Discussion of Winterbottom's sign (posterior cervical lymphadenopathy) as an early indicator of CNS involvement in West African sleeping sickness.
26:57 Antigenic Variation: Christina explains how T. brucei evades the host immune system through antigenic variation, specifically by changing its variant surface glycoprotein (VSG) coat.
31:06 Traditional studies The hosts discuss how, in the past, studies have been focusing on parasites in the blood.
33:30 The hosts discuss how this paper challenges the paradigm.
34:35 Paper's Main Point: The paper's central hypothesis is that extravascular spaces are major reservoirs of antigenic diversity, crucial for the parasite's ability to evade the immune system.
35:54 Figure 1 Analysis: Discussion of Figure 1, which shows increased VSG diversity in tissues compared to blood at different time points post-infection.
40:43 Key Finding: Almost 90% of expressed VSGs in any individual infection were found exclusively in extravascular spaces.
41:44 Figure 2 Discussion: Examination of Figure 2, demonstrating that common VSGs appear in tissues first and that tissues contain more unique VSGs than blood.
47:09 Figure 3 Analysis: Discussion of Figure 3, showing that parasites are cleared more slowly from tissues than from blood.
49:19 Experimental Setup: The study uses experimental animals (mice) infected with a small number of trypanosomes (5) to track VSG expression dynamics.
51:22 Figure 5 - Delayed Clearance and Diversity: Explanation of Figure 5, which demonstrates that delayed parasite clearance in tissues (using IGG knockout mice) leads to increased VSG diversity.
56:33 Conclusion and Discussion: The hosts summarize the paper's findings, highlighting the importance of tissue spaces in parasite diversification and immune evasion, and they discuss open questions and future research directions.