Episode 26: Tamara Franklin, PhD

The following interview was conducted in-class, during the Spring 2024 session of Hidden Figures: Brain Science through Diversity, taught by Dr. Adema Ribic at the University of Virginia. What follows is an edited transcript of the interview, transcribed by Zachary Alexander Johnson, Pearce Cabell, Marcello Enzo Massimo, Annika Victoria Fread, Xuan Kim Tran, Natalia Weber Leaf, Peyton Samantha Yee, Zian Zhou, Amisha Geeta Sahni, Hayly Y-nhi Nguyen, Julia Juyoung Park, Jayati R. Maram, and Avani Kalimili, who also drafted Dr. Franklin’s biography. The final editing was by Dr. Adema Ribic.

Dr. Tamara Franklin is an Associate Professor in the Department of Psychology and Neuroscience at Dalhousie University. She completed her PhD at the Swiss Federal Institute of Technology and her postdoc at the European Molecular Biology Laboratories’ Mouse Biology Unit. Her laboratory researches the brain function required to drive social interactions in order to understand the neural mechanisms responsible for neurodevelopmental and psychiatric diseases characterized by severe social impairments such as Autism Spectrum Disorder and Alzheimer’s disease. Her lab uses neural tracing, optogenetic, chemogenetic, and in vivo electrophysiological techniques to understand how epigenetic regulation affects social-related functional connectivity within neural circuits.

How did you know you wanted to pursue psychology and neuroscience?

When I was a kid, I was really into crime movies and thought I wanted to be a forensic psychologist – I wanted to be like Clarice Starling from The Silence of the Lambs, be in the FBI, and work with serial killers. I ended up going into the Psychology and Neuroscience program at Dalhousie University to pursue clinical psychology. But, as I started taking more neuroscience classes, I ended up really enjoying the neuroscience field. I realized I’d never want to do clinical psychology as a career, and I would much prefer to do neuroscience.

How did you discover you wanted to look into the brain functions of social behaviors?

I started out working in stress research, and that’s what I started for my undergrad thesis. Then, throughout my masters, I started to focus on environmental enrichment and the long term impact of environmental manipulation. I started by looking at anxiety and depressive behaviors, but the issue with those behavioral tests is that they’re always a bit artificial in some ways. I started to see that more of the social behaviors were more relevant to what the animals would normally be doing in their environment instead of needing to be artificially manipulated. I started to look at naturalistic behaviors and started to think about how it might be a better read out than some of the more artificial tests that we do. This is what drew me into social behaviors. I enjoy spending time with mice and seeing how they interact with each other, and there’s a lot we can learn from that sort of naturalistic behavior.

Have you experienced any challenges associated with managing and juggling all the responsibilities of your multiple projects as well as directing your lab?

There's definitely challenges. Maybe it would be easier to have everybody in the lab focused on a single project and doing exactly the same topic, but I just find various things interesting and then always end up looking at other different things that come to my mind. The challenge, of course, is the literature, as the literature is huge. The literature on any topic is just ballooning and it’s really hard to keep track when there’s papers coming out every day. Also for the lab, it’s nice when everyone in the lab is working on the same thing because everyone can have exciting conversations about the same results. So sometimes, when people are working on very different projects, it makes it a little bit harder to make the lab cohesive. There are benefits, obviously, because you get to look at things you’re interested in and also attract students who might be interested in different topics.

Reading your past research about the effect of epigenetic regulation on social behavior has been so fascinating. Could you please talk about your current projects and what techniques you are implementing?

The one that is the most focused on epigenetics is looking at social hierarchy and social rank to see how natural hierarchies are formed in a regular colony cage and observing the differences between dominant and subordinate animals within the cage. The project focuses on studying the gene expression of an epigenetic regulator, HDAC2, which has been associated with changing gene expressions of a wide range of synaptic plasticity genes, mostly related to learning and memory.

Could you elaborate more on the natural hierarchies observed?

We observed that middle rank animals really stood out as being different from the dominant or subordinate mice. I thought that this could be associated with cognitive flexibility, because if you are always dominant, all of your social interactions are as the dominant. And if you are subordinate, all of your social interactions are as the subordinate. But if you are somewhere in the middle, it’s going to depend on the animal that you are up against, right? So, needing that flexibility to maneuver between being subordinate and being dominant within a pair requires a different brain function and ability, which is the idea of what we have been working on. This summer, we’re going to directly test that by testing the cognitive flexibility capabilities of these middle ranked animals if they are used to being able to switch processes.

Is there a specific aspect of your research that you're most excited about?

So the other project that we're working on right now is looking at the long term effects of adolescent stress, and we’ve seen increased anxiety-like behaviors. But we’ve also seen reduced maternal care behavior, so we’re trying to link adolescent stress with later risk for postpartum depression. We finished looking at maternal care data, but right now we are analyzing data that looks at depressive-like behaviors, like self-care, and motivational behaviors during that postpartum period to see if we could use that sort of adolescent stress model as a model for later risk of postpartum depression and the changes that occur during pregnancy and how that interacts with previous stressful experiences. It’s pretty neat, and that’s just what we have been collecting data for and analyzing at the moment, so it’s probably the most exciting thing right now.

What type of tests do you use in the laboratory in the context of your postpartum research?

Right now we are focused on the more depressive side and less on the anxiety side. We were looking at the splash test, which is where you spray a kind of sticky solution on the mouse’s back, and then look at the latency for them to start grooming it off and the amount of grooming they do. This can be used as a measure of self care. We also did foraging tasks, where you give them sunflower seeds with peels on them, and you can see the level of motivation for working for the seed since work is needed to peel them, and then they scatter the seeds for future planning. There is both motivation for a food reward and future planning in this foraging test. We also ran a normal forced swim test, which is for depressive-like behavior. We looked at the nest building and maternal care behavior, such as scoring three times a day across multiple days during the postpartum period and looking at the amount of time they spend with their pups.

What is your take on adolescent stress in terms of whether it is positive or negative for the individual?

I don’t know the answer to that, but I would like to study it more. Intuitively I would like to say it should promote resilience. Our stress paradigm is very strong and our mice show pretty serious anxiety-like behaviors as adults. Whether we can titrate that down to show the opposite, I’m not sure.  I'm not quite sure how to do this as a controlled experiment yet in terms of the the timing during the adolescent period. I haven't quite figured out how to do this in a way where we're not doing a ton of experiments with a ton of animals. And I have a feeling that's why there's not a ton of studies that have done this before either, because it's kind of a hard question to get at.

How has your research contributed to the understanding of Alzeihmer’s disease and how it manifests in the brain?

In the Alzheimer's project, we were really focusing on social behaviors associated with Alzheimer’s. In Alzheimer’s disease, there is social inappropriateness, social withdrawal, as well as aggression. These behaviors are less well-studied in preclinical mouse models because people are usually focused on learning and memory deficits, but social symptoms are actually one of the biggest concerns for both the patient and caregivers, which is why we were focusing on that. Of course there are other labs starting to do this as well, so we’re trying to characterize mouse models of Alzheimer’s in those behaviors and we also did in vivo electrophysiology recordings to look at local field potentials. I am currently looking to do single unit analyses of these recordings to look at brain responses to social and non-social orders and see if there are differences in the Alzhiemer’s mouse models to see the underlying electrophysiological differences of social processing in the cortex.

How has your research contributed to the understanding of Autism Spectrum Disorder and how it manifests in the brain?

For autism, we’re looking at a maternal immune activation model, which is a model that’s used to look at perinatal infection and the length between perinatal infection with later autism risk. In this project, we just started working with the model and the paper is hopefully going to come out soon but we haven’t published it yet so we don’t really know of long ranging impact, but it is mostly looking at immune mediators resulting from that model. The prenatal infection model is a bit murky as everyone is using slightly different injection protocols as well as immune agents, so the field is a bit confusing at the moment. That is why we are trying to add to in order to better characterize the model

Are there any studies you would like to revisit?

I do have one project that hasn't been funded, which I have tried more than once now. I can’t exactly remember what the experiment was, but it was an enriched environment and a standard environment, and we were trying to reverse the effects of early stress with an enriched environment. We had them in the enriched environment for a long time and then we had them in an enriched environment for a short time. But to sacrifice the animals at the same time meant the short term enriched environment had to go back into standard housing and then we would sacrifice them all at the same time. What we saw, though, was that just in the control animals, when you have the animals in an enriched environment go back to standard housing, they actually showed really high depressive behaviors after having this big jump. So then I started thinking about how housing conditions could impact all of our research. We always think about our standard housing and how it is in a relatively impoverished environment, but the brain background of all our information is not quite correct, because it’s in the background of a fairly impoverished environment.

I was interested in this because in Alzheimer’s disease there’s evidence that people who have very high cognitive function and very demanding jobs have a delay in the start of Alzheimer’s disease, but then once they get diagnosed with Alzheimer’s, their decline is way quicker. There’s been this sort of paradox of them holding off longer, but then once they have it, they have a very quick decline. And so, I was wondering if that’s because they’re in an enriched environment with a certain level of brain activity, and then as you start in these early stages of Alzheimer’s, everything sort of declines, such as stopping work, social network gets smaller, and all sorts of stimulation declines quite a bit in the environment. It’s that change from a very active environment to a not so active environment that then causes this swift decline and that would cause an even swifter decline than just being in standard housing the whole time. So I really want to look at this as maybe when we’re looking at Alzheimer’s, we’re looking at mechanisms working within the wrong background of brain activity. And so if we could model this quick decline, it would be interesting to see how to better find even your therapeutic targets and how it could all be acting very differently in this situation.

What are some of the challenges that you've observed with acquiring funding?

In Canada, it's extremely challenging. We have probably about a 10 to 15% success rate on a lot of them.

You just try, try, try again. How I deal with it is mostly talking to colleagues. Everyone commiserates and we’re all in the same boat. I try now to send my grant application drafts to as many people as possible to possibly increase my chances of success, but that’s really all you can do.

What notable awards or distinctions have you earned throughout your academic career?

I haven’t won very many awards in my career. I have been recognized by another University for my work in EDI. But generally, I would say the most meaningful things are when students say that they appreciate my work. That gives us a bit of a lift to keep going right through all the other kinds of negative aspects of the job. We always like it when we get positive feedback from the trainees.

Are you particularly proud of any personal achievements, inside or outside of the lab?

Well, the lab just got funded for another 5 years from one of our federal councils, so that was good, because that was my first renewal of that grant, and it’s from an agency that people in my field depend on in Canada. So if you lose that funding, it makes things very difficult, so it’s great that I am set for another 5 years. That just happened last week so it’s the one that comes to mind first, but when our paper gets accepted, hopefully soon, I’ll move on to that one.

Are there any significant rejections that you can remember? And how were you able to make those experiences of professional growth?

I mean, there's just so many grant rejections. You have your list of unfunded and then another folder of funded grants, and the unfunded one is very long while the funded is quite short. I don’t really dwell on singular comments. You’ll always get angry at some of the reviewer comments here or there, but I try not to etch them into my brain. So you gotta be happy with the ups and then not so sad with the downs.

How has your research experience differed between Switzerland and Italy?

In Switzerland, you could practically dream up any experiment and just go ahead and do it, which was great and quite different from when I was a graduate student in Canada. They also had a very different sort of work ethic and work environment where when you went to do your PhD, you signed a work contract with the university, and it was like a real 9 to 5. In Italy, I was at the EMBL, which is the EU research institution, which was a very supportive environment.

What did you learn from your experiences in Switzerland and Italy?

From those places I learned to establish  really clear expectations and set targets and milestones in my lab to make sure that we maintain productivity without necessarily feeling like we have to be there 24 hours a day. So I think that those sorts of experiences help to see a different way of doing things.

Have you ever experienced instances of discrimination in your academic or professional life?

I have had difficulties working with some people here and there, and in those instances you just had to talk it out as best you can and then try to avoid those people as much as you’re able to. I try to make sure I have people that I can talk to and ask for their opinion in regard to the situations so that I can get input and see what they would do.

What resources do you have as a professor that allow you to address workplace discrimination?

At my university, we do have a black faculty and staff caucus that are there to advocate for black staff and faculty on campus. The only other thing I can think of is sometimes you have to be careful with the student evaluations because there's such a wide range of people in the classes. But I mean there’s nothing much you can do about those sorts of issues apart from doing your best to advocate for others.

What are some things you wish you knew earlier when starting your journey?

One of the nice things about academia is how you go through the stages and gradually learn more about the profession. When you get to your own lab, you’ve already seen various iterations of the labs and different ways of working. Nothing was a total surprise, since you have experience with different supervisors and colleagues talking about the field. But you learn so much through the whole process. In undergraduate, I didn't think I had fully grasped what animal research was. When I got into the lab and started working with animals, I hadn’t fully grasped the toll it would take to sacrifice the animals, so that was a big shock in the beginning. As you go through the stages of your career, you accumulate all this information that when you get to your own lab, it’s not so shocking.

Did you have any inspiring figures or people who helped you get where you are today?

I’ve had great mentors throughout my career. My undergraduate mentor first got hired when I started my undergraduate, so she was really enthusiastic and excited about setting up the lab. Through that, I was able to experience seeing the beginning of the lab set up and imagine what it would be like to set up my own lab. Generally throughout my career, there have been a lot of people who have been really supportive. I’ve had a lot of women mentors as well, such as my PhD program supervisor. She was really great at maneuvering within a system. Of course, the people in my life, like my family, were also very helpful. In terms of professional mentors, people like my thesis supervisors have been really supportive.

What advice do you have for students who want their work to be recognized by their supervisors?

Supervisors love seeing results. So I would start that relationship very quickly where you’re just going to them and showing them everything, like things that don’t work, things that do work, and just having a lot of conversations with them and making sure that you have expectations clearly laid out between the two of you. You can say that you would like to have meetings once a week, once every two weeks, if possible, and just have that conversation with them to start the relationship so that you have a good back and forth.

How can students advocate for themselves on a larger scale?

Student groups are really important to be able to bounce ideas off one another in case you run into problems with your supervisor, so at least you have other people that you can talk to who maybe have navigated through it and have a better idea of what works and what doesn’t. It’s important to have because the other students you meet and work with right now could be your colleagues in 20 years if you stay in the field. I still have many friends and colleagues that I met doing undergraduate research, so it’s important to establish that network.

Did you ever have doubts or points of uncertainty in your professional or academic journey?

I’m a bad person to ask these sorts of questions because I started and have been in neuroscience and never took a year off. I was just completely neuroscience all the way, so I never really considered leaving neuroscience or leaving academia. I did have some issues when I moved to Switzerland. I worked in a bigger lab and German cultures can tend to be a bit more hierarchical than I was used to, so it felt a bit more constrained in a way. So for the first couple months, I didn’t know if I could continue working there forever, but then I did talk to my supervisor and she sorted it out so it was fine. In the end, it was just a moment of hesitation, but once I talked it through, everything was totally fine.

What advice would you give to students interested in a career in research?

Based on my perspective, the people who perform best at research tend to be not that emotional. Research can be quite challenging as it can be draining because of the high and lows involved. And you have to have other things in your life other than the high and lows in research. You have to take it for what it is. Many people who get into research are really high-performingso they get good grades. You are able to control how well you’re going to do in our school system. In research, you don’t necessarily get the results based on the amount of effort you put into it. No matter the work that is put in, the experiment has the possibility to fail and it may not be your fault. Essentially, you need to be aware of that and be able to deal with it because things do not always work even though you worked super hard.

How would you describe the immediate future of neuroscience?

I think it's a good time for neuroscience. I’ve been in it now for around 20 years and it feels like it goes in leaps. Right now I feel like neuroscience is at one of these leaps, because the tools have been developing so fast over the past 5 to 10 years. I think there are all sorts of questions that can be answered in a way that we couldn’t before, so I think we’re in an exciting phase.

What future directions do you see for neuroscience?

For future directions, of course all sorts of AI will be huge in neuroscience. I think we’re really going to have to start integrating more computational work into everything. Even for me, I do behavior, but now everyone’s running a lot of behavioral data through an AI software, so we are definitely being forced to get better at programming

How do you see artificial intelligence having an impact on your work?

Nowadays, everything's going to these AI-based softwares to count your cells, run your behavior, and do imaging. It just seems like it's heading in that direction. And so it's something our undergraduate neuroscience programs are really going to have to start to integrate or focus on educating  the students to have a little bit of a better grasp of the computer science side.

How do you think the advancements and technology imaging and genetic sequencing alongside AI has influenced the neuroscience field?

From what I can tell, it allows us for more unbiased approaches. Up until this point we just couldn't deal with that amount of data. So we had to just pick and choose the specific things that we are interested in. But now with AI, I feel like you can just analyze way more stuff with a totally unbiased approach. So going forward, we could potentially start to see totally different new things that we haven't begun to think about.

Are there any breakthroughs in molecular technology  in particular that you think will be especially important for epigenome research, specifically as it relates to social-related neural circuitry?

Currently, we still don't have a great way of targeting epigenetic marks to parts of the genome exactly in the way that we'd like to, which causes issues with providing causal evidence for epigenetic regulation, which is important. I mean, it is possible, but it's not done easily, and it's not something that just any lab can  implement. But there's definitely people working on it, so I would say it's a matter of time.

How do you imagine connectomics research being translated further into mice studies?

There's just a ton to be done right now. You can do whole-brain imaging with a functional imager, but then we're still probing individual pathways. Usually first trying one pathway and then trying one cell-specific aspect of that pathway. So it's very tedious in a sense, because we're essentially pathway by pathway, trying to figure out what each pathway does in this contribution. So yes, I feel like we have a ton of work that can still be done, especially now that we're getting down to such cell type specific, pathway specific and then multiple pathways at the same time.

Is there any particular therapeutic application to your work that you're really looking forward to? Or are you just more interested in the sort of hard science behind it?

I'm more of a hard science person, but some of the applications in terms of the in vivo electrophysiology  work have effects of modulating brain activity in people. And so the hope is always that we would find changes in brain activity that could be manipulated in a way that could ameliorate symptoms. That's probably the most direct clinical application I can think of to my work as well as potential pharmacological targets that are looked at as well.

What are some things you like to do for fun outside of your lab? Are there any hobbies that you enjoy?

So I have 2 dogs which is great. I like to knit, which is not super exciting, but very relaxing. Other than that, it's mostly just hanging out with friends and trying to get some time away. Of course, I have my work colleague friends, but I also have friends who have nothing to do with neuroscience. And so that's always good to hang out with people who don't know anything about neuroscience, and probably won't mention it at all in an evening. So that's always good to separate yourself too.

How do you establish a balance between your professional career and your personal life?

I just try to be really organized. So I have short term goals, long term goals, and I keep like a gazillion lists that I cross things off of. While I'm working I'm very efficient. I don’t take breaks at work but I try to get home by 5. So it's just a way of organizing time as best as you can, and prioritizing. Oftentimes you do have to say no to some things, especially when you know you are stretched. So you also have to be a little bit selective in the stuff that you agree to do.

Are there any neuroscience topics that you find fascinating outside of your realm of research?

I really like learning about the developments in brain-computer interface research and following that stuff.  In Switzerland, they had a guy who was paralyzed and they were able to connect an exoskeleton to his spinal cord so that he can walk again. So he's almost part-robot, part-person and regaining a lot of function. And that's kind of how I started getting into in-vivo electrophysiology. I just thought it was so neat that you could essentially translate brain activity to the physical world.

Having had the unique experience of seeing your PI set up their own lab when you were an undergraduate student, do you believe this prepared you for when the time came for you to set up your own lab?

I think it's emotionally hard because it's so slow. While training I was always in labs where I was setting up new things so it's not really the setting up of a new thing that was difficult. It's that you're setting up everything, and you have pressures to get your research going. So you know you are going to have to apply for a grant really soon, you are going to have to show something, and with everything, there's so much sort of bureaucracy and things that slow you down.

When you just began your research journey, how did you come to terms performing studies on animals and having to sacrifice them?

You just kind of get used to it. When you understand the processes, and the concept of humane endpoints as well as why this research is important, everything seems a little bit better. With that being said I was  vegetarian for about 15 years of my life, because I thought it kind of balanced the animal use for research vs. the animal use for personal reasons.

Are there any steps that you take in your lab to make animal handling more ethical?

In my lab, I kind of steer away from a lot of transgenic work, because that does involve animals that end up not being directly used in an experiment. And I do find that hard. Additionally, we're always trying to optimize by finding other tests to use to replace stressful or by trying to make sure that we're using as few animals as we can. But it's definitely something as a lab that we're always conscious of.

How do you think treatment strategies for Alzheimer’s disease will develop in the future?

The older we live, the more neurodegenerative diseases we're going to have. We may not get to a point where we cure Alzheimer's, but if we could just delay the onset or delay the progression a bit in everyone, that would be huge. I don't know how close we are to that; it's hard to tell. I feel we could also probably do a lot better in improving non-pharmacological treatment approaches, in terms of our living conditions and support systems for people living with Alzheimer's. I feel like we have a good idea of how people living with Alzheimer's can be better supported, which is a start.

Do you think the pervasiveness of technology use in the young generation increases stress and depression, especially given the notable plasticity of our brains at that age?

It's gonna be interesting to see the long term effects of all of this. There has definitely been debate over whether online forms of social communication are just as good as in person. Attention span is most definitely decreasing, but in terms of stress that teens are experiencing, obviously there was a huge cohort of teens that just went through COVID so that's going to be interesting to see how that resolves itself. There are 2 sides of it. It can be more damaging in the sense that it's a plastic time. But also it's a plastic time, and maybe you can rebound better than when stress happens in adulthood. And so that's something that we're thinking about trying to start working on as well. Whether everything is maladaptive, or if there's some long term implications for stress during adolescence that could actually build some forms of resilience. So I don't think stress is always negative in the long term.

What advice would you give to someone applying to neuroscience PhD programs outside of the United States?

They're all very different. But I think for most of them it's still best to contact the Supervisor directly, and once you have the supervisor on board, then they can tell you how best to actually apply to the program. So I would usually start with the researchers that you most want to work with and contact them.