11 research outputs found
Annotated Cell and Molecular Biology 5e: What We Know and How We Found Out
https://dc.uwm.edu/biosci_facbooks_bergtrom/1013/thumbnail.jp
Basic Cell and Molecular Biology 5e: What We Know and How We Find Out
https://dc.uwm.edu/biosci_facbooks_bergtrom/1014/thumbnail.jp
The impact of Alu elements on the human proteome
Approximately 45% of the human genome is comprised of mobile, or transposable,
DNA elements (TEs). Of this, 11% is attributed to Alu elements. Alu elements are
approximately 300 base pairs in length and are primarily located in the introns of
non-coding DNA. However, in some cases, the introduction of an alternative splice
site, as a result of an Alu insertion in a protein-coding region, leads to the exonisation
of a partial Alu sequence. This exonisation can lead to the expression of an
alternative protein isoform which may have disrupted or altered function and
therefore, could have the potential to be cause disease.
Through the use of bioinformatics, this project firstly aimed to predict the extent of
Alu exonisation and subsequent translation in the human proteome. Additionally,
through the use of local sequence alignments, the nature of observed insertions could
also be studied. Once prior aims were established, a series of techniques were used
to study the possible effects of translated Alu insertions on the structure and function
of proteins. A number of protein variants were expressed and purified from E. coli.
Using biophysical techniques, such as ITC and CD, Alu structure and any effects of
Alu insertions on the ligand binding and stability of MBP were studied. Additional
binding experiments were performed as a means to explore a potential binding
interaction between an Alu-like sequence with geldanamycin, an interaction which
was initially observed using phage display.
A secondary avenue of research was performed in collaboration with the Aspden
and Wurdak groups at the University of Leeds to investigate the difference in
translation levels of âAluâ and ânon-Aluâ mRNAs in human cells. Analysis was
performed using a combination of polysome profiling, reverse transcription and
quantitative PCR
ENZYMES: Catalysis, Kinetics and Mechanisms
Onemarvelsattheintricate designoflivingsystems,andwecannotbutwonderhow life originated on this planet. Whether ?rst biological structures emerged as the selfreproducing genetic templates (genetics-?rst origin of life) or the metabolic universality preceded the genome and eventually integrated it (metabolism-?rst origin of life) is still a matter of hot scienti?c debate. There is growing acceptance that the RNA world came ?rst â as RNA molecules can perform both the functions of information storage and catalysis. Regardless of which view eventually gains acceptance, emergence of catalytic phenomena is at the core of biology. The last century has seen an explosive growth in our understanding of biological systems. The progression has involved successive emphasis on taxonomy ! physiology ! biochemistry ! molecular biology ! genetic engineering and ?nally the large-scale study of genomes. The ?eld of molecular biology became largely synonymous with the study of DNA â the genetic material. Molecular biology however had its beginnings in the understanding of biomolecular structure and function. Appreciationofproteins,catalyticphenomena,andthefunctionofenzymeshadalargeroleto play in the progress of modern biology
Drug development progress in duchenne muscular dystrophy
Duchenne muscular dystrophy (DMD) is a severe, progressive, and incurable X-linked disorder caused by mutations in the dystrophin gene. Patients with DMD have an absence of functional dystrophin protein, which results in chronic damage of muscle fibers during contraction, thus leading to deterioration of muscle quality and loss of muscle mass over time. Although there is currently no cure for DMD, improvements in treatment care and management could delay disease progression and improve quality of life, thereby prolonging life expectancy for these patients. Furthermore, active research efforts are ongoing to develop therapeutic strategies that target dystrophin deficiency, such as gene replacement therapies, exon skipping, and readthrough therapy, as well as strategies that target secondary pathology of DMD, such as novel anti-inflammatory compounds, myostatin inhibitors, and cardioprotective compounds. Furthermore, longitudinal modeling approaches have been used to characterize the progression of MRI and functional endpoints for predictive purposes to inform Go/No Go decisions in drug development. This review showcases approved drugs or drug candidates along their development paths and also provides information on primary endpoints and enrollment size of Ph2/3 and Ph3 trials in the DMD space