Javidlab:research

From OpenWetWare

(Difference between revisions)
Jump to: navigation, search
Line 33: Line 33:
|- valign="center"
|- valign="center"
-
|style="color: #FFFFFF; background-color: #930000; width: 200px"|
+
|style="color: #FFFFFF; background-color: #930000; width: 200px; height: 150px"|
<div style="clear: right; text-align: center; float: none color:#ffffff; ">
<div style="clear: right; text-align: center; float: none color:#ffffff; ">
<font size="5">  
<font size="5">  
Line 51: Line 51:
|- valign="center"
|- valign="center"
-
|style="color: #FFFFFF; background-color: #000079; width: 200px"|
+
|style="color: #FFFFFF; background-color: #000079; width: 200px; height: 150px"|
<div style="clear: right; text-align: center; float: none color:#ffffff; ">
<div style="clear: right; text-align: center; float: none color:#ffffff; ">
<font size="3">  
<font size="3">  
Line 70: Line 70:
|- valign="center"
|- valign="center"
-
|style="color: #FFFFFF; background-color: #000079; width: 200px"|
+
|style="color: #FFFFFF; background-color: #000079; width: 200px; height: 150px"|
<div style="clear: right; text-align: center; float: none color:#ffffff; ">
<div style="clear: right; text-align: center; float: none color:#ffffff; ">
<font size="3">  
<font size="3">  
Line 91: Line 91:
|- valign="center"
|- valign="center"
-
|style="color: #FFFFFF; background-color: #000079; width: 200px"|
+
|style="color: #FFFFFF; background-color: #000079; width: 200px; height: 150px"|
<div style="clear: right; text-align: center; float: none color:#ffffff; ">
<div style="clear: right; text-align: center; float: none color:#ffffff; ">
<font size="3">  
<font size="3">  
Line 112: Line 112:
|- valign="center"
|- valign="center"
-
|style="color: #FFFFFF; background-color: #000079; width: 200px"|
+
|style="color: #FFFFFF; background-color: #000079; width: 200px; height: 150px"|
<div style="clear: right; text-align: center; float: none color:#ffffff; ">
<div style="clear: right; text-align: center; float: none color:#ffffff; ">
<font size="3">  
<font size="3">  

Revision as of 09:30, 4 July 2013



Home     Research     Publications     Lab Members     Lab Alumni     Fun Stuff     Contact


OVERVIEW

Tuberculosis causes more deaths globally, and in China, than any other single pathogen. Some of the reasons for its success are the ability of the causative organism, Mycobacterium tuberculosis, to lie undetected in the host for decades (clinical latency), the very long treatment times for successful antibiotic treatment (phenotypic resistance) and emerging drug resistance to effective antibiotics. The Javid laboratory is interested in investigating some of the fundamental physiological mycobacterial processes that may contribute to these phenotypes.



Adaptive
Mistranslation

We have previously shown that the protein translation error rate (mistranslation rate) in mycobacteria is unusually high. Importantly, manipulation of the error rate, both up and down, appears to have profound effects on antibiotic phenotypic resistance. We have shown that mycobacterial strains with high error rates have remarkable phenotypic resistance to the antibiotic rifampicin, and the opposite is true for high fidelity mutants. We are interested in investigating the basic mechanism for these observations, and identifying other potentially adaptive phenotypes that arise from low translational fidelity.



Mycobacteria
host-pathogen
interactions

The majority of people infected with M. tuberculosis – almost a third of the world’s population – do not become ill unless their immune system weakens. This suggests that mycobacteria have evolved to evade host immune responses, much like other chronic infections. We are interested in investigating the mechanisms by which mycobacteria manipulate the host environment to their own ends. We use a variety of approaches – including proteomic profiling of mycobacteria-infected cells, flow cytometry and forward genetics to address these questions.



Protein
Translation
Fidelity

The lab’s interest in protein translation fidelity arose from our observation regarding ‘adaptive mistranslation’ in mycobacteria (see above). We are extending these findings to other organisms and systems to determine the mechanisms by which organisms may tune translational fidelity.



GatCAB dependent
tRNA synthesis
and protein evolution

Unlike eukaryotic cytosols, the majority of bacteria and archae utilise a two-step, indirect pathway to make amino-acylated glutamine and/or asparagine tRNA. To ensure fidelity of the genetic code, physiologically misacylated tRNAs (Glu-tRNAGln and Asp-tRNAAsn) are recognised by the heterotrimeric enzyme GatCAB, and through a transamidation reaction, synthesise the cognate amino-acyl tRNA. The lab is interested in determining the biochemistry of this process in mycobacteria and applying that to investigate ‘statistical proteome’ analysis in mycobacterial physiology.




Room 4-302 Biotech Building
School of Medicine
Tsinghua University

Personal tools