Protein synthesis FAQ

Certainly. We're keenly exploring extracellular vesicles as mediums for cells to communicate. These cell made vesicles often carry microRNAs and other non-coding RNAs, presenting a unique avenue to understand how neurons modulate their environment, which is especially interesting in neurological conditions. We are exploring extracellular vesicles as these tools with which cells can communicate and transfer gene expression patterns. And we're looking at, for example, how early life brain tumours such as medulloblastoma can impact neuron development and activity and how this can affect later life pain processing and neurological conditions. This has been possible via funding from the Medical Research Foundation, which supported a big collaboration between the labs of Gareth Hathway, Beth Coyle, Vicky James, Anna Grabowska and myself in Nottingham.

I foresee a shift where RNA will gain more traction, considering recent successes in RNA-based therapies. Given the role sncRNAs play in axons, our research aligns well with this trend. By understanding the axonal RNA biology, we can pave the way for targeted therapies that could revolutionize how we approach various neurological conditions.

As an analogy, when the axon is scaled up to be the arm in a human body, you can think of the axon length in relation to the neuron's cell body as the equivalent distance from Nottingham to Paris. This significant length poses a logistical challenge for the neuron. For proteins to be expressed at the axon terminal, which is distant from the cell body, there's a requirement for translation regulation. In other words, there is a need for descentralized gene expression. Here, small non-coding RNAs play a pivotal role. Our work on microRNAs has shown their importance in spatial-temporal control of gene expression. This research aligns with the current interest in RNA biology and offers potential avenues for drug discovery, especially given the advances in RNA technologies post-covid.

At its core, pain involves sensory neurons that extend axons from their cell bodies into peripheral tissues and the spinal cord. Understanding these sensory terminals, especially their responses under various conditions such as inflammation, is pivotal. Our Axon-RNA-centric approach allows us to detect RNA changes and leverage them to alter sensitized states, providing a more accessible avenue for drug targeting.

Events like ELRIG 2023 are incredibly insightful. Although I'm aware of the academia-industry interface through collaborations, for instance with Eli Lilly, attending such events on a larger scale opens up a new perspective. The goal is to bridge the gap between fundamental science academics and the broader investment realm without losing focus on the core mechanisms. By attending, I hope to identify more opportunities for collaboration and application.

A significant collaboration is with the Versus Arthritis Pain Center in Nottingham, in particular with Vicky Chapman and Gareth Hathway. Initially, my work wasn't focused on pain research, but joining forces with experts from this center led half of my lab's work to be directed towards pain-related projects. Another meaningful collaboration involves studying motor neuron diseases alongside Prof. Rob Layfield and Dr. Dan Scott. This collaboration allows us to leverage our expertise in RNA and neuron development and apply it to conditions like motor neuron disease.

In a typical neuron, the cell body comprises only about 10-20% of the cytoplasm; the rest lies in the axon and dendrites. Thus, understanding neurons requires acknowledging the axon's role. We advocate for the research focus to consider this polarization and complex structure. By highlighting different transcriptomics within axons versus cell bodies and targeting their regulation, we can influence the entire neuron's functioning, potentially transforming treatment approaches.

My lab primarily focuses on neuroscience, but we approach problems from the perspective of axon biology. We're deeply interested in how neurons develop, undergo polarization and establish/maintain connectivity. This understanding helps not only in the development of the nervous system but also sheds light on age-related degeneration linked to the loss of axon connectivity. We use various cellular models, such as compartmentalised microfluidic neuronal cultures, to study how axons face different environments compared to cell bodies. Within this context, our research is focused on RNA biology, specifically the role of non-coding RNAs or microRNAs in regulating local axon protein synthesis. This knowledge is especially valuable when exploring different diseases and conditions like pain or neurodegeneration.

Success in research demands passion. It's crucial to find a subject that genuinely interests you and dedicate yourself to it. While there may be long periods where the efforts don't seem to yield desired or meaningful outcomes, perseverance is key. When success does come, it's a deeply rewarding experience. Hold onto that feeling.

While we've initiated dialogues on integrating AI, it hasn't transformed our work yet. However, I see it as a significant tool, especially for handling and processing big data. AI can help bridge the expertise gap in understanding both bioinformatics and biological terms, aiding in the efficient mining of information.

Some of the common side effects include:

Antineoplastic protein synthesis inhibitors are indicated for the treatment of chronic or accelerated phase chronic myeloid leukemia with resistance and/or intolerance to two or more tyrosine kinase inhibitors.

Antineoplastic protein synthesis inhibitors are a class of drugs used to treat adults with chronic or accelerated phase chronic myeloid leukemia (CML; a type of cancer of the white blood cells) who have already been treated with at least two other medications for CML and can no longer benefit from these medications or cannot take these medications because of side effects. CML is a rare, slow-growing type of cancer of the bone marrow—the spongy tissue inside bones where blood cells are made. CML causes an increased number of white blood cells in the blood. Signs and symptoms may include:

This person has naturally red hair. Why is this hair red instead of some other color? And, in general, what causes specific traits to occur? There is a molecule in human beings and most other living things that is largely responsible for their traits. The molecule is large and has a spiral structure in eukaryotes. What molecule is it? With these hints, you probably know that the molecule is DNA.

The way scientists look at disease variants is to compare the genetic makeup of a large number of people who have a specific disease with those who do not. This allows scientists to look for genetic variants that are more common in people with a disease compared to people without the disease. For example, if a particular genetic variant is present in 80 percent of patients with the disease but only 20 percent of the healthy population it suggests that this variant is increasing the risk of that disease. However, looking for a disease that is caused by variants in a single gene is the simplest example. There are many complex diseases where variants in many different genes might be involved. As well as the transcriptional and translational regulation of some enzyme production may vary due to the genetic variation in the enhancer and repressors of a gene. So, for this type of comparison to be effective very large groups of people need to be studied, usually in the tens of thousands, to find the variants that have subtle effects on disease risk. Researchers also try to pick individuals with similar phenotypes, in both the diseased and healthy groups, so that the disease genes are easier to identify and study.

Using a gene to make a protein is called gene expression . It includes the synthesis of the protein by the processes of transcription of DNA and translation of mRNA. It may also include further processing of the protein after synthesis. Gene expression is regulated to ensure that the correct proteins are made when and where they are needed. Regulation may occur at any point in the expression of a gene, from the start of the transcription phase of protein synthesis to the processing of a protein after synthesis occurs. The regulation of transcription is one of the most complicated parts of gene regulation in eukaryotic cells and is the focus of this concept.

The genetic code consists of the sequence of nitrogen bases in a polynucleotide chain of DNA or RNA. The bases are adenine (A), cytosine (C), guanine (G), and thymine (T) (or uracil, U, in RNA). The four bases make up the “letters” of the genetic code. The letters are combined in groups of three to form code “words,” called codons . Each codon stands for (encodes) one amino acid unless it codes for a start or stop signal. There are 20 common amino acids in proteins. With four bases forming three-base codons, there are 64 possible codons. 61 codons are more than enough to code for the 20 amino acids, thus more than one codon codes for a single amino acid. Please find genetic codes in Table \(\PageIndex{1}\) or in appendix 1 .

The human genome refers to all the DNA of the human species. Human DNA consists of 3.3 billion base pairs and is divided into more than 20,000 genes onto 23 pairs of chromosomes. The human genome also includes noncoding sequences (e.g. intergenic region) of DNA, as shown in Figure \(\PageIndex{2}\).