Immunology and Infectious Disease Commons^™

On The Construction And Interpretation Of Fitness Landscapes For Hiv: A Computational Perspective, Elizabeth Grace Johnson

Doctoral Dissertations

To identify vulnerable viral targets to incorporate into an immunogen, fitness landscapes for the viral proteome have been constructed. These landscapes describe the sum or synergistic replicative cost exacted on the virus for any combination of non-synonymous mutations. Here we attempt to assess the robustness of current computational methods for measuring the fitness cost of HIV polymorphisms in these landscapes. We also address in the following chapters assumptions and shortcomings that may underlie current landscape's uneven ability to predict fitness effects.

In the first chapter, I appraise the robustness of current frame-works that derive fitness costs from patient sequence data. …

Transmission Pattern Of Major Clonal Lineages Of Toxoplasma Gondii, Pooja Saraf

Doctoral Dissertations

Toxoplasma gondii is the most successful zoonotic pathogen known today. One-third of people are chronically infected worldwide. Different strains of T. gondii shows variability in mouse virulence which may potentially correlate with disease manifestation in humans. As a result, mouse is used as the model organism to study the virulence of T. gondii strains. To study the virulence on a global scale, it is necessary to establish a standardized approach for mice virulence assays. Thus, we review the methodologies used in different labs and put forth standardized approaches to study the T. gondii virulence in mice (Chapter 1). Recent …

Notch1 Modification And Signaling In T Helper Cell Differentiation, Karthik Chandiran

Doctoral Dissertations

Notch signaling modulates the developmental program of multiple cell types. The cleaved intracellular region of the receptor possess the functional domain which influences T cell activation, proliferation and differentiation. However, in naïve CD4 T cells the mechanistic details underlying cleavage of Notch1 is not clearly understood. Notch functions by acting as a signaling hub and interacting with its canonical (CSL) and non-canonical (NFkB, mTOR, Akt) binding partners to cross-talk with other signaling pathways. Notch signaling drives the differentiation program of multiple T helper cell subsets (Th1, Th2, Th17, Th9, iTreg and TFH). Recent discoveries also demonstrated a role for microRNAs …

Characterization Of Protein A And Sortase A In Staphylococcus Pseudintermedius: Potential Targets For Novel Therapeutic Approaches, Manasi Balachandran

Doctoral Dissertations

Staphylococcus pseudintermedius is an opportunistic pathogen in dogs and is the most frequent cause of canine pyoderma. The recent emergence of methicillin resistance and multidrug resistance has made it increasingly difficult to treat infections using conventional antibiotics. There is an urgent need for alternative strategies to prevent S. pseudintermedius infections. The development of a successful vaccine against S. pseudintermedius is complicated by several virulence and immune evasion factors. The objective of this project was to identify new targets for treatment and prophylaxis of methicillin-resistant and multidrug-resistant S. pseudintermedius infection. This was achieved using two strategies (a) understanding the roles of …