자료유형  

 학위논문

Control Number  

0017164179

International Standard Book Number  

9798346759331

Dewey Decimal Classification Number  

574.191

Main Entry-Personal Name  

Rana, Ushnish.

Publication, Distribution, etc. (Imprint  

[S.l.] : Princeton University., 2024

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2024

Physical Description  

111 p.

General Note  

Source: Dissertations Abstracts International, Volume: 86-06, Section: B.

General Note  

Advisor: Panagiotopoulos, Athanassios Z.;Brangwynne, Clifford P.

Dissertation Note  

Thesis (Ph.D.)--Princeton University, 2024.

Summary, Etc.  

요약Biomolecular condensates, which are phase separated assemblies of proteins and nucleic acids, have emerged as a new paradigm behind the spatiotemporal organization of the cellular interior. Understanding the biophysical principles driving the phase behavior of these biomolecules is of fundamental importance for deciphering the biological function of these structures.It has been well established that the phase behavior of biological condensates is highly sensitive to the sequence of the phase separation capable proteins. However, there are still open questions regarding how sequence specificity drives condensation. In this work, I first addressed how protein sequence can drive the phase equilibria of condensates towards aggregation instead of phase separation. Utilizing a simple lattice model of disordered proteins alongside Grand Canonical Monte Carlo simulations, we establish an approximate order parameter that distinguishes whether a protein sequence phase separates or aggregates. Building on our knowledge of sequence order parameters, I then address how both protein sequence and oligomerization together influence the behavior of multicomponent multiphasic condensates. Our results show that large sequence differences between disordered proteins are required for driving the formation of multiple demixed phases, suggesting that other mechanisms might be at play behind the formation of endogenous multiphasic condensates. Instead, differential oligomerization of disordered proteins can cause demixing and formation of multiphasic condensates. Furthermore, I validate our simulations by performing in vivo reconstitution experiments. Our results highlight how asymmetric oligomerization and sequence patterning underlie the formation of multiphasic condensates. I expect these results to be of potential significance for the design of de novo condensates for synthetic biology. Given the interest in developing new engineered condensates for metabolic engineering, I also investigated how condensate composition and interaction architecture influence exchange across their interfaces. I find that increasing affinity be-tween a protein scaffold and its client molecules causes interfacial exchange to slow down substantially beyond a threshold interaction strength.Taken together, the findings presented in this dissertation further our understanding of the biophysical principles behind the formation of biological condensates. These results would enable future studies that aim to engineer for synthetic biology applications as well as those aimed at drugging endogenous condensates for therapeutic applications.

Subject Added Entry-Topical Term  

Biophysics.

Subject Added Entry-Topical Term  

Chemical engineering.

Subject Added Entry-Topical Term  

Bioengineering.

Index Term-Uncontrolled  

Phase equilibria

Index Term-Uncontrolled  

Biomolecular condensates

Index Term-Uncontrolled  

Disordered proteins

Index Term-Uncontrolled  

Biological condensates

Added Entry-Corporate Name  

Princeton University Chemical and Biological Engineering

Host Item Entry  

Dissertations Abstracts International. 86-06B.

Electronic Location and Access  

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Control Number  

joongbu:657417