[CCoE Notice] Cullen College Dissertation Defense Announcement - Garima Singh

[Hutchinson, Inez A]

[Dissertation Defense Announcement at the Cullen College of Engineering]
Systematic Design of Pulse Dosing to Eradicate Persister Bacteria
Garima Singh
July 17, 2023;   10:00 AM -12:30 PM

Room: Chemical Engineering Conference Room (S234)
Via Teams: Join here.<https://urldefense.com/v3/__https:/teams.microsoft.com/l/meetup-join/19*3ameeting_NTA5NTFmNTgtYzkxOS00OTY1LTllZTUtOTI0Y2JkMWVmMTU4*40thread.v2/0?context=*7b*22Tid*22*3a*22170bbabd-a2f0-4c90-ad4b-0e8f0f0c4259*22*2c*22Oid*22*3a*22143979f0-9ccc-40ab-b176-171cd2e4e5e7*22*7d__;JSUlJSUlJSUlJSUlJSUl!!LkSTlj0I!EQrU1VcT9dOOkxlbFE8a8Pxj9zoMyFXYnlWo3LFyDBJWYFdqkukLo-kVDvWWz1LFgPnAzLhcIVCNdEZRIMsTKrNlmfSnaCk$>

Committee Chairs:
Michael Nikolaou, PhD
Committee Members:
Jacinta Conrad, Ph.D. | Mehmet Orman, Ph.D. | Marzia Cescon, Ph.D. | Vincent Tam, Ph.D
Abstract
          Persister bacteria are a major threat to human health. Such bacteria use clever mechanisms to survive otherwise lethal exposure to antibiotics and resume normal activity upon antibiotic removal. They are implicated in many chronic infections and in relapse of infections such as tuberculosis and recurrent urinary tract infections. In fact, prolonged persistence catalyzes the emergence of complete antimicrobial resistance. A key question, then, is how to capitalize on persister dynamics in a way that achieves eradication of these bacteria. A challenge to that end is insufficient knowledge about mechanisms of persister dynamics.
          Aiming to address this problem, the main hypothesis of this research is that it is feasible to design effective dosing regimens against persisters based on empirical, if incomplete, mathematical models. Recent studies have confirmed that pulse dosing, if designed appropriately, can indeed be effective. However, effective pulse dosing design has been mainly handled by trial and error, requiring relatively extensive experimentation. In this dissertation, methods for rapid systematic design of effective pulse dosing have been developed. We derive design formulas that explicitly characterize the shape of generally effective or optimal periodic pulses. These methods were tested through computer simulations and in vitro experiments on different classes of antibiotics, as well as on prior literature data. In all cases, the outcomes on persister bacteria eradication predicted by our method were confirmed. We further developed a method for simulating and testing clinically relevant dosing profiles paving path for in vivo translation of pulse dosing to treat persister bacteria.
          In addition to the above, an experimental platform entailing a microfluidic device was developed to track bacteria at single cell level to probe further into the dynamics of persisters.
[Engineered For What's Next]

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