Let me tell you about our newest preprint – a story of heat shock and prenylation in Plasmodium falciparum! biorxiv.org/content/10.110…
[Thread]
Most people with malaria get fever - how do malaria parasites survive that stress? /1
First of all, P. falciparum has a ton of heat shock proteins. In particular the DnaJ/Hsp40 family is very expanded – there are 49 Hsp40 family members in P. falciparum!! /2
We have previously found that one of these Hsp40s in Plasmodium is farnesylated – that is, modified by a 15-carbon isoprenyl group. We call it HSP40 and it is the canonical Hsp40 in malaria parasites. /3
Guess what? If you inhibit farnesylation OR total synthesis of #isoprenoids – parasites can’t tolerate temperature changes any more. Inhibitors + heat/cold shock = dead parasites! 🦠+🔥=💀/4
So, these inhibitors are likely to be even better in sick people than they are in vitro (and they’re already pretty good).. and probably block mosquito transmission (a cold shock).
Many more details in the preprint – looking forward to feedback! /fin
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With fellowship interview season coming up, time to look in the mirror and retake the Harvard Implicit Association Test. Takes <10 min, and IMHO should be required for all academic selection committees:
We’ve been collaborating w/Cindy Dowd at GWU (@GWtweets) making new antimalarials called MEPicides = cool prodrugs that target the DXR enzyme of the MEP pathway -- an essential biosynthetic pathway that humans and other mammals just don’t have/2
Turns out, malaria parasites aren’t the only bugs with the MEP pathway. We were totally inspired by Dan Beiting @hostmicrobe@pennvet – they found that staphylococci have either the mevalonate pathway (like people) or the MEP pathway (like parasites)/3
@CHOP_ID@CHOP_Research We consider most infections polymicrobial, even though only 6.7% actually grew >1 organism. Common bugs in kids with surgical cultures?
☑️S. aureus (MSSA and MRSA)
☑️Group A strep
☑️other resp/oral colonizers (Hflu/S. milleri)
/3
@CHOP_ID Calf exposure is such a big risk b/c calves are very likely to have #crypto. My favorite outbreak is this 2013 overturned cattle truck carrying 100s of calves. RR for diarrhea 3.0 in first responders who "carried calves":
New article on the "leaky pipeline" of #WomeninSTEM. Once female faculty get their first big grant, they tend to stay in science - yay! But...[thread] pnas.org/content/early/…
Senior author Greenberg is quoted in @nature: "[Women] should realize that, sure, it is not easy in academia, but they are not going to have any more difficulty than men once they get their first grant.” nature.com/articles/d4158…
Given the percentages of women in leadership positions, in named professorships, and even full professors at many institutions, this seems a surprising conclusion. Our own institution has had equal # of women medical trainees for >15 yrs - not reflected in our leaders.