Fake Nuclei, Microbial Communities, and Graduate School: A Conversation with Gordon Pherribo (Taga Lab)

By: Joseph Maa

I’ve recently had the opportunity to sit down with Gordon Pherribo, a current graduate student in the Taga Lab at Berkeley studying vitamin B12 in bacterial communities.[1] Throughout history, bacterial communities have constantly been scrutinized under researchers’ microscopes, but as microscope resolution has improved, researchers increasingly are only limited by their technical knowledge and the ingenuity of their experiments.

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Figure 1: Gordon Pherribo, bacteria whisperer, who studies vitamin B12 as a model nutrient to study nutrient sharing within microbial communities. Picture credits: Joseph Maa

The central motif of vitamin B12 is it’s corrin ring, a cyclic four ring system that resembles heme, the main oxygen carrying component of our red blood cells. Vitamin B12 is an organic compound that is required in limited amounts by our bodies. However, Vitamin B12 is produced only by bacteria. For this reason, studies on Vitamin B12 biosynthesis and how the bacteria share B12 are critical to human health. Pernicious anemia, a condition in which an insufficient amount of red blood cells is produced, is caused by intestinal inability to pick up B12. [2]  B12 is structurally composed of an upper and lower ligand, (an ion bound to a metal atom) and the lower ligand can affects how much B12 is made. [3][4]

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Figure 2: Figure: Vitamin B12 with its characteristic corrin ring. Different species of bacteria produce various lower ligands, some of which have been found to be intermediates of other ligands [5]
Furthermore, he shared his experiences in research, both his current experiences adjusting to the rigor of graduate school, and his past experiences with finding mentorship in classes. However, simply describing his achievements does not do him justice.

Sitting down with the man himself is quite a unique experience. His upbeat, enthusiastic voice is tinged with a slight New Jersey accent that carries across the room. As we struck up conversation before the interview, I could sense a genuine sense of curiosity emanating from his interest in his research, as well as excitement at the opportunity to share his experiences doing so. To give you a better impression of his inherent curiosity, his present motivation for studying the micro biome today originated from watching Discovery Channel when he was smaller, plopped down in front of the TV. His mother wholeheartedly nurtured and encouraged his pursuit of a sciences as she “need[ed] her children to support themselves”.

As an undergraduate, Gordon started off his research in a genetics lab in the summer of his freshman year, transitioning to a RNA protein lab in his sophomore summer, looking at stabilization of mRNA transcripts. Moreover, he continued to traverse vastly different subjects in biology as a junior and senior. From studying laminin, an extracellular matrix protein, to characterizing virulence in streptococcus pneumonia, Gordon took the opportunity to explore many different segments of the natural world.

His current research currently covers the following mysteries:

  1. Using vitamin B12 as a model nutrient to study nutrient sharing within microbial communities
  2. Looking in bacterial communities for benevolent bacteria that export B12 into the environment, and the relationships between different members of the community.
  3. In the future, possible translational work with nutrient sharing in other communities, to better understand how bacterial community compositions change over time. Theoretically, this could lead to insights in developing new antibiotics or utilizing synthetically useful bacterial species to increase productivity of key goods.

Personally, one of the fears that I had with academia in general was the sheer difficulty of understanding biological science research. With such a steep entry learning curve of entry, not only is it difficult for students to approach topics that they are curious about, but also, academics also tend to become highly specialized due to the complexity of biological systems. However a critical problem arises due to this specialization: while there are vast reserves of content for aspiring scientists to read, there exists many fewer resources teaching aspiring biologists how to break down complex material into manageable chunks.

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Figure 4:  “Science is it’s own language, you have to give it time” -Gordon [6]
When reading research papers, Gordon recommended doing the following:

  1.  First, make sure you know what you want to get out of a research paper before reading it. Is it for background information? Methods? What do you want to get out of the paper?
  2.  Secondly, don’t be afraid when reading papers from outside your field. As you become more accustomed to the field, you get a feel for the field and don’t have to read every introduction. However, when you’re just starting out, it’ll be difficult.
  3.  Thirdly, when first learning, stick to reviews. As you start to understand the subtleties of the field, start looking at the references that the papers cited.
  4.  Finally, science is it’s own language – you have to give it time to settle in!

Lastly, I asked Gordon about any standout papers that he had read recently. From one science nerd speaking to another, I’m always on the lookout for different scientific perspectives to listen to. Gordon’s face lit up and he began referencing a paper published on protein structures that resembled nuclei. (Chaikeeratisak, Nguyen, Khanna et al. 2017[7] The salient points of the paper are included here:

  1. After the bacteria Pseudomonas was infected with a specific bacteriophage: 201φ2-1, a protein structure developed that morphologically resembled a nucleus and acted like one (contained transcription and replication proteins, but not translation proteins)
  2. Because bacteria are prokaryotes, which by definition means they don’t have nuclei, this was an incredibly surprising find.
  3. The nucleus-like structure was attached to a tubulin spindle on both sides (bipolar), dubbed PhuZ. PhuZ is essential to formation of the nucleus like structure
  4. The viral capsids dock to the nucleus-like structures and the nucleus-like structure appears to package DNA into the capsids.

I don’t capture the absolute beauty that this paper really inspires, but here are a few pictures from their paper.

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Figure: Cryo-electron tomography displaying the nucleus-like protein (gp105 in blue) and the capsid particles surrounding it. The 3d image is created by adding slices of the layers together to get a compelling picture. (Chaikeeratisak, Nguyen, Khanna et al. 2017[7]
Their results are stunning and the cryo-electron tomography work that they did is incredibly exciting. It’s moments like these that really captivate the hearts and minds of nascent biologists everywhere.

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Figure: Different proteins from different cell processes are shown on the left. Notice that translation and nucleotide synthesis machinery exist outside the nucleus-like structure (appears to be a void), while DNA replication and transcription take place within the nucleus-like structure, which is one of the defining traits of a nucleus! The various gp proteins are homologs to components of their respective processes (e.g. for DNA replication, gp197 is a helicase homolog). On the right, you can clearly see the red nucleus-like structure protein surrounding the DNA (blue) and rest of the information is fairly superfluous (as you probably will only remember the key concepts!) (Chaikeeratisak, Nguyen, Khanna et al. 2017[8]
I highly recommend checking out their supplementary videos that the paper listed [9] since I can’t host videos here. If you do watch the video, look for formation of the nucleus like structure for yourself, spinning across the cell from one side of the cell into the middle!

Finally, I can’t be more grateful to have the opportunity to interview an up-and-coming scientist, so shout-out to Gordon Pherribo and Professor Taga for letting me do these interviews, and look forward to more coming soon!

Your friend,

Joseph Maa

 

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