Everyone's least favorite lab mate
@kepatitis-c.bsky.social
I much prefer the sharpest of criticism of a single intelligent man to the thoughtless approval of the masses
- Johannes Kepler
“It is a damn poor mind indeed which can't think of at least two ways to spell any word.”
-Andrew Jackson
- Johannes Kepler
“It is a damn poor mind indeed which can't think of at least two ways to spell any word.”
-Andrew Jackson
I almost forgot
November 20, 2025 at 10:13 PM
I almost forgot
This work highlights how interactions between MGEs can produce unique effects where both benefit from their nested existence. Furthermore, we have extended TnpB’s mechanism that sheds light on why TnpB is so successful.
November 20, 2025 at 10:12 PM
This work highlights how interactions between MGEs can produce unique effects where both benefit from their nested existence. Furthermore, we have extended TnpB’s mechanism that sheds light on why TnpB is so successful.
So we did a similar experiment with conjugative plasmids and found that IS605 provides offensive and defensive benefits to conjugative plasmids, acting like a primitive anti-self defense mechanism to spread plasmids between cells.
November 20, 2025 at 10:12 PM
So we did a similar experiment with conjugative plasmids and found that IS605 provides offensive and defensive benefits to conjugative plasmids, acting like a primitive anti-self defense mechanism to spread plasmids between cells.
Moreover we also noticed that IS605 tended to cluster in conserved plasmid regions of conjugative plasmids.
November 20, 2025 at 10:12 PM
Moreover we also noticed that IS605 tended to cluster in conserved plasmid regions of conjugative plasmids.
And specifically it is the RNA-guided nuclease activity that is responsible for this benefit - confirming our hypothesis!
November 20, 2025 at 10:12 PM
And specifically it is the RNA-guided nuclease activity that is responsible for this benefit - confirming our hypothesis!
Which we were able to show experimentally by competing plasmids in a displacement assay. We see plasmids that contain an IS605 have an enormous advantage over those that don’t, despite the IS itself being detrimental to plasmid replication
November 20, 2025 at 10:12 PM
Which we were able to show experimentally by competing plasmids in a displacement assay. We see plasmids that contain an IS605 have an enormous advantage over those that don’t, despite the IS itself being detrimental to plasmid replication
But in the context of plasmids this results in a newly inserted IS605 to reprogram TnpB to target, and destroy, all IS- plasmids within the cell. With no competition only IS+ plasmids will replicate, biasing their inheritance.
November 20, 2025 at 10:12 PM
But in the context of plasmids this results in a newly inserted IS605 to reprogram TnpB to target, and destroy, all IS- plasmids within the cell. With no competition only IS+ plasmids will replicate, biasing their inheritance.
So what is going on? TnpB happens to be the ancestor to Cas12 and is also an RNA-guided nuclease. The @sternberglab.bsky.social lab figured out TnpB uses this activity to promote genomic retention by cutting excision scars - preventing IS loss.
November 20, 2025 at 10:12 PM
So what is going on? TnpB happens to be the ancestor to Cas12 and is also an RNA-guided nuclease. The @sternberglab.bsky.social lab figured out TnpB uses this activity to promote genomic retention by cutting excision scars - preventing IS loss.
But not all IS families followed this trend. The IS605 family deviates while its close cousin IS200 does not. This suggests that IS605 has a unique interaction with plasmids, with the additional gene carried by IS605, TnpB, likely being responsible.
November 20, 2025 at 10:12 PM
But not all IS families followed this trend. The IS605 family deviates while its close cousin IS200 does not. This suggests that IS605 has a unique interaction with plasmids, with the additional gene carried by IS605, TnpB, likely being responsible.
Well they can just have more shots on goal. We found a consistent relationship between the chromosomal copy number of an IS co-occurrence on plasmids. The more you try the more you are likely to succeed (poetic I know).
November 20, 2025 at 10:12 PM
Well they can just have more shots on goal. We found a consistent relationship between the chromosomal copy number of an IS co-occurrence on plasmids. The more you try the more you are likely to succeed (poetic I know).
Insertion Sequences (IS) are enriched in plasmids. Which is quite curious as plasmids often have multiple copies preventing efficient inheritance of IS+ plasmids. So how do ISs come to be on plasmids in the first place?
November 20, 2025 at 10:12 PM
Insertion Sequences (IS) are enriched in plasmids. Which is quite curious as plasmids often have multiple copies preventing efficient inheritance of IS+ plasmids. So how do ISs come to be on plasmids in the first place?
What is the best strategy to win any contest?
Eliminate your opponents of course.
Recently, my friend @fernpizza.bsky.social showed how plasmids compete intracellularly (check out his paper published in Science today!). With @baym.lol, we now know they can fight.
www.biorxiv.org/content/10.1...
Eliminate your opponents of course.
Recently, my friend @fernpizza.bsky.social showed how plasmids compete intracellularly (check out his paper published in Science today!). With @baym.lol, we now know they can fight.
www.biorxiv.org/content/10.1...
November 20, 2025 at 10:12 PM
What is the best strategy to win any contest?
Eliminate your opponents of course.
Recently, my friend @fernpizza.bsky.social showed how plasmids compete intracellularly (check out his paper published in Science today!). With @baym.lol, we now know they can fight.
www.biorxiv.org/content/10.1...
Eliminate your opponents of course.
Recently, my friend @fernpizza.bsky.social showed how plasmids compete intracellularly (check out his paper published in Science today!). With @baym.lol, we now know they can fight.
www.biorxiv.org/content/10.1...
When I was told I’d have a summer undergrad I couldn’t have imagined how lucky I would be. Hue has no tolerance for the easy way out and takes on new challenges with an infectious positivity. One day (hopefully🤞) someone will be just as lucky to have her as a grad student. We will miss you!
August 8, 2025 at 7:11 PM
When I was told I’d have a summer undergrad I couldn’t have imagined how lucky I would be. Hue has no tolerance for the easy way out and takes on new challenges with an infectious positivity. One day (hopefully🤞) someone will be just as lucky to have her as a grad student. We will miss you!
I apparently deleted a important “TnpA” label from my poster so now my week is ruined but if you want to help search for more mistakes and you are at the Microbial Populations GRC come see me Wednesday
July 6, 2025 at 6:55 PM
I apparently deleted a important “TnpA” label from my poster so now my week is ruined but if you want to help search for more mistakes and you are at the Microbial Populations GRC come see me Wednesday
Reposting with an eye catching figure because I forgot
April 24, 2025 at 10:15 PM
Reposting with an eye catching figure because I forgot
In a humanized mouse model our VLPs effectively generated CAR T cells in vivo that were subsequently able to treat a B cell leukemia even better than traditional ex vivo CAR T cells.
April 24, 2025 at 9:59 PM
In a humanized mouse model our VLPs effectively generated CAR T cells in vivo that were subsequently able to treat a B cell leukemia even better than traditional ex vivo CAR T cells.
Finally, we incorporated co-stimulatory ligands on the surface of the VLPs to create a T cell targeted VLP capable of selectively generating and activating CAR T cells in vitro.
April 24, 2025 at 9:59 PM
Finally, we incorporated co-stimulatory ligands on the surface of the VLPs to create a T cell targeted VLP capable of selectively generating and activating CAR T cells in vitro.
So we spliced the measles envelope with that of the related Dolphin Morbillivirus to create a chimera that maintained fusogenicity with reduced response to measles vaccinated serum.
April 24, 2025 at 9:59 PM
So we spliced the measles envelope with that of the related Dolphin Morbillivirus to create a chimera that maintained fusogenicity with reduced response to measles vaccinated serum.
However, using the measles envelope for in vivo delivery poses a challenge as most of us are immunized against the virus (for the moment that is), so would be neutralized preventing the delivery of cargo. However other related viral envelopes evade anti measles antibodies.
April 24, 2025 at 9:59 PM
However, using the measles envelope for in vivo delivery poses a challenge as most of us are immunized against the virus (for the moment that is), so would be neutralized preventing the delivery of cargo. However other related viral envelopes evade anti measles antibodies.
But we found that scFvs overall impede surface expression and function of the MeV envelope. Nanobodies (i.e. llama antibodies) on the other hand can effectively re-target the MeV envelope without preventing expression.
April 24, 2025 at 9:59 PM
But we found that scFvs overall impede surface expression and function of the MeV envelope. Nanobodies (i.e. llama antibodies) on the other hand can effectively re-target the MeV envelope without preventing expression.
We started with the measles virus envelope that can be redirected using to a receptor of choice with the addition of a targeting domain - usually an scFv.
April 24, 2025 at 9:59 PM
We started with the measles virus envelope that can be redirected using to a receptor of choice with the addition of a targeting domain - usually an scFv.
Greatful to have been given the opportunity to present my wacky little project at @crisprmeeting.bsky.social and thanks to @baym.lol and the rest of the lab for the support!
February 20, 2025 at 11:05 PM
Greatful to have been given the opportunity to present my wacky little project at @crisprmeeting.bsky.social and thanks to @baym.lol and the rest of the lab for the support!