Regulation of membrane fusion by Tlg2p & Vps45p through the endosomal system of Saccharomyces cerevisiae

SNARE proteins are essential components of the machinery that facilitates membrane fusion in eukaryotic cells. SNARE proteins are subject to multiple levels of regulation, one of which is imbedded in the syntaxin (Qa-SNARE) molecule. It has been demonstrated that some syntaxins adopt a closed conformation, whereby an autonomously folded N terminal domain (the Habc domain) forms intramolecular contacts with the SNARE domain; this conformation precludes complex assembly. The Sec1p / Munc18 (SM) family are a conserved group of proteins that regulate membrane fusion through interactions with their cognate syntaxins. Formulation of unifying hypotheses describing how SM proteins function has been problematic, primarily due to the multiple modes of interaction that have been characterised for different members of this family binding to their cognate SNARE proteins. The yeast SM protein Vps45p regulates membrane fusion through the trans-Golgi / late endosomal system, and interacts directly with the syntaxin (Tlg2p) and the v-SNARE (Snc2p) proteins. Vps45p also binds to the assembled SNARE complex of Tlg2p, Vti1p, Tlg1p and Snc2p. In this thesis I demonstrate that the Habc domain of Tlg2p has an inhibitory effect on SNARE complex formation. This is an important finding, as whether or not Tlg2p adopts a closed conformation has hitherto been controversial. Furthermore, I have demonstrated that the inhibitory effect of the Habc domain on complex formation can be alleviated by Vps45p in vitro. In addition to investigating the functional significance of Vps45p’s interaction(s) with Tlg2p, I have also investigated binding of the SM protein to the v-SNARE Snc2p. I have demonstrated that the affinity of Vps45p for Snc2p is weaker than either of the modes of interaction characterised between Vps45p and Tlg2p. Finally, I have developed an in vitro fusion assay to enable us to dissect the functional significance of the various interactions that Vps45p displays with its cognate SNARE proteins

Graphical connection priming and ethics: As our sense of human connection decreases, so too does our ethical decision-making.

From road rage to youtube comments, there are indications all around us that when there is some form of human disconnect, we are far from the best versions of ourselves. A recent paper revealed that the mere thought of human disconnection can weaken our morals. This paper reveals three new experiments that further explore this phenomenon. The results of experiments 1 and 2 show that an increase of unethical decision-making can be triggered via simple imagery of stickmen separated from one another. Experiment 3 suggests that the phenomenon might also be triggered with simple geometric imagery depicting the disconnection of 2D shapes

Avatars, disconnecting agents: exploring the nuances of the avatar effect in online discourse

A recurring theme in the study of unethical and harmful behavior is disconnection. And therefore perhaps it is no surprise that when individuals view themselves as a separate entity, they can loosen or even lose their moral compass. This phenomenon is known as the avatar effect. The experiment reported here explores the avatar effect in online communities. It explores whether participants adopt the suggested traits of a given entity when they communicate via that entity. The results revealed that participants' youtube comments were significantly influenced by their username and profile image, despite being asked to give their own opinion. The paper offers further insight into the growing field of disconnecting agents and compromised ethics

The Money Consensus: What do people really think of the monetary system? And does it influence ethical decision-making?

Recent experiments have revealed that the mere thought of money can decrease ethical decision-making. This paper explores the underlying mechanisms of this phenomenon by investigating how the modern generation feels about the monetary system. Data from US and UK participants revealed that over 80% felt that money is one of the leading reasons why people make unethical decisions. The general consensus included that the invention of money has been mainly bad for the environment, plants, and wildlife, and that humans would have more authentic relationships and be happier and more ethical if money had never been invented. The findings offer valuable insight into why thoughts of money can loosen our morals

The Gilgamesh Effect: The ethical consequences of disconnection

A number of recent experiments have revealed that the mere thought of human connection can increase ethical-decision making whereas the thought of human disconnection can decrease ethical decision-making. This paper provides an appropriate name for the phenomenon, reviews the evidence, and highlights its relevance

The Middleman Effect: The ethical consequences of paying others to act on one's behalf

In a time where we are increasingly made aware of unsustainable and unethical corporations, it is important to ask why consumers continue to purchase their products? Why aren't more people 'voting' with their dollar and demanding higher environmental and ethical standards? Is it simply a lack of awareness or are there also underlying factors that increase our tolerance to unethical conduct? This paper reveals a phenomenon that shares similarities to the bystander effect: the middleman effect. The results of Experiment 1 reveal that participants are more likely to purchase unethical products if there are more middlemen involved in the manufacturing process. Experiment 2 reveals that while maintaining the same number of middlemen in a given situation, it is significant when the unethical conduct takes place in a series of linear events; as the unethical conduct gets closer to the point of purchase, the tolerance of unethical behaviour decreases. The middleman effect may be an important part of the puzzle which facilitates those around the world striving for an ethical and sustainable future

Lexicon connection priming and ethics: As our sense of human connection decreases, so too does our ethical decision-making

In an era increasingly surrounded by images, it is all too easy to overlook the power of the humble word. Recent studies have shown that images depicting human disconnection can weaken our morals. This paper reveals three new experiments that demonstrate that words can replicate this phenomenon. The results of experiments 1 and 2 show that an increase of unethical decision-making can be triggered via lexicon primes that convey the idea of human disconnection. Experiment 3 suggests that while priming the idea of human disconnection can loosen our morals, priming the idea of human connection can increase ethical decision-making. The three experiments also indicate that the primes are more effective when they are indirect (such as via the use of metaphors), and when they are created to seemingly appear to come from the participants themselves (such as asking participants to list evidence for a given statement)

The Avatar Effect: The harmful consequences of decision-making through a 'separate' entity.

As we are in the midst of a global crisis, caused primarily by human activity, it is vital to ask, what leads us to make such ethically compromised decisions? This paper reveals a phenomenon that may cause an individual to loosen or lose their moral compass: the avatar effect. The case is made that there are frequent situations where individuals can make decisions through—what appears to them as—a separate entity, and that through compounding underlying mechanisms, this can result in an increased sense of disconnection, compromised judgement, and harmful consequences

Money, a disconnecting agent: Reminders of money trigger a feeling of disconnection which increases the likelihood of unethical decisions.

For eons many have hypothesized the corrupting influence of money, and yet, there has been a great void in the way of empirical experimentation. However, a series of pioneering experiments has begun to show confirmation of previous assumptions, one of which showed that the mere thought of money can loosen morals. This paper reveals three new experiments that explore the underlying process of this phenomenon. The results of experiments 1 and 2 suggest that individuals primed with money are less ethical than both a control group and individuals primed with business-related concepts. Further questioning revealed that an underlying mechanism behind the unethical decisions may be a decreased feeling of human connection. In accordance with this finding, the results of experiment 3 demonstrate that priming with disconnection themes directly results in a greater likelihood of unethical decisions

Climate Psychology: What is preventing the uptake in lifestyle changes that would significantly reduce one’s environmental impact?

Human consumption and human emissions are rapidly destroying our home planet and the vital ingredients of life—the science is clear and abundant. And so, we need to make extreme changes in many aspects of life as quickly as possible—as a matter of survival. This paper explores the underlying mechanisms that prevent the public from making lifestyle changes that would significantly reduce their environmental impact. As part of the experiment, students were asked to complete the same anonymous survey. Before starting they were reminded that there is no right or wrong answer and that they should give their honest opinion. Perhaps the most reassuring of the findings was that over 90% of both UK and U.S. participants stated that they were concerned about the climate crisis and that they felt that it is important to make lifestyle changes to reduce harmful emissions, thus indicating a general awareness and motivation to take personal action. The most common reasons cited for not wanting to make a suggested lifestyle change were that the participant felt as though it is difficult to make the suggested change, and that the participant felt that the suggested change would not make a significant difference. Accordingly, the opposite statements were the most common reasons given for why the participants would consider making a suggested lifestyle change (it is easy to make the suggested change, and the participant felt that the suggested change would make a significant positive impact). The paper concludes by offering some ways in which we could facilitate the uptake in sustainable lifestyle choices